MutationT @ ster 2025

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Known disease mutation: ClinVar ID 3948 (pathogenic)
Protein features (might be) affected

Model: simple_aae
Tree vote: 86|14 (del | benign) ?
Automatic classification due to ClinVar

Analysed issue

Analysis result

Variant

Chr11:57614474C>A (GRCh38)

Gene symbol

Gene constraints

LOEUF: 0.23, LOF (oe): 0.09, misssense (oe): 0.77, synonymous (oe): 0.87 ? (gnomAD)

Ensembl transcript ID

ENST00000378324.6

Genbank transcript ID

UniProt / AlphaMissense peptide

IC1_HUMAN | AlphaMissense: transcript, gene

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.1240C>A
g.17088C>A

AA changes

AAE:	R414S	?
Score:	110

Frameshift

No

Length of protein

Normal

Pathogenic variant (ClinVar)

Hereditary C1 esterase inhibitor deficiency - dysfunctional factor

pathogenic

Variant DBs

	Not in dbSNP
	Allele 'A' was not found in gnomAD

Protein conservation

Species	Match	AA	Alignment
Human		414	E	A	A	A	A	S	A	I	S	V	A	R	T	L	L	V	F	E	V	Q	Q	P	F	L
mutated	not conserved	414	E	A	A	A	A	S	A	I	S	V	A	S	T	L	L	V	F	E
Ptroglodytes	no homologue
Mmulatta	no homologue
Fcatus	no homologue
Mmusculus	no homologue
Ggallus	no homologue
Trubripes	no homologue
Drerio	no homologue
Dmelanogaster	no homologue
Celegans	no homologue
Xtropicalis	no homologue

Protein features

Start (aa)	End (aa)	Feature	Details
23	500	CHAIN		lost
409	415	HELIX		lost

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	0.771	1
	3.231	1
(flanking)	6.208	1

?

Splice sites

No abrogation of potential splice sites predicted by MaxEntScan.

Distance from splice site

N/A

Kozak consensus sequence altered?

No

poly(A) signal

N/A

AA sequence altered

Yes

Chromosome

11

Strand

1

Original gDNA sequence snippet

CCTCCGCCATCTCTGTGGCCCGCACCCTGCTGGTCTTTGAA

Altered gDNA sequence snippet

CCTCCGCCATCTCTGTGGCCAGCACCCTGCTGGTCTTTGAA

Original cDNA sequence snippet

CCTCCGCCATCTCTGTGGCCCGCACCCTGCTGGTCTTTGAA

Altered cDNA sequence snippet

CCTCCGCCATCTCTGTGGCCAGCACCCTGCTGGTCTTTGAA

Wildtype AA sequence

MLFVEPILEV SSLPTTNSTT NSATKITANT TDEPTTQPTT EPTTQPTIQP TQPTTQLPTD
SPTQPTTGSF CPGPVTLCSD LESHSTEAVL GDALVDFSLK LYHAFSAMKK VETNMAFSPF
SIASLLTQVL LGAGENTKTN LESILSYPKD FTCVHQALKG FTTKGVTSVS QIFHSPDLAI
RDTFVNASRT LYSSSPRVLS NNSDANLELI NTWVAKNTNN KISRLLDSLP SDTRLVLLNA
IYLSAKWKTT FDPKKTRMEP FHFKNSVIKV PMMNSKKYPV AHFIDQTLKA KVGQLQLSHN
LSLVILVPQN LKHRLEDMEQ ALSPSVFKAI MEKLEMSKFQ PTLLTLPRIK VTTSQDMLSI
MEKLEFFDFS YDLNLCGLTE DPDLQVSAMQ HQTVLELTET GVEAAAASAI SVARTLLVFE
VQQPFLFVLW DQQHKFPVFM GRVYDPRA*

Mutated AA sequence

MLFVEPILEV SSLPTTNSTT NSATKITANT TDEPTTQPTT EPTTQPTIQP TQPTTQLPTD
SPTQPTTGSF CPGPVTLCSD LESHSTEAVL GDALVDFSLK LYHAFSAMKK VETNMAFSPF
SIASLLTQVL LGAGENTKTN LESILSYPKD FTCVHQALKG FTTKGVTSVS QIFHSPDLAI
RDTFVNASRT LYSSSPRVLS NNSDANLELI NTWVAKNTNN KISRLLDSLP SDTRLVLLNA
IYLSAKWKTT FDPKKTRMEP FHFKNSVIKV PMMNSKKYPV AHFIDQTLKA KVGQLQLSHN
LSLVILVPQN LKHRLEDMEQ ALSPSVFKAI MEKLEMSKFQ PTLLTLPRIK VTTSQDMLSI
MEKLEFFDFS YDLNLCGLTE DPDLQVSAMQ HQTVLELTET GVEAAAASAI SVASTLLVFE
VQQPFLFVLW DQQHKFPVFM GRVYDPRA*

Position of stopcodon in wt / mu CDS

1347 / 1347

Position (AA) of stopcodon in wt / mu AA sequence

449 / 449

Position of stopcodon in wt / mu cDNA

1485 / 1485

Position of start ATG in wt / mu cDNA

139 / 139

Last intron/exon boundary

1231

Theoretical NMD boundary in CDS

1042

Length of CDS

1347

Coding sequence (CDS) position

1240

cDNA position

1378

gDNA position

17088

Chromosomal position

57614474

Speed

0.32 s

All positions are in basepairs (bp) if not explicitly stated differently. cDNA/gDNA/chromosomal position: Ins/del are shown as 'last normal base / first normal base'.
AA/aa: amino acid; CDS: coding sequence; mu: mutated; NMD: nonsense-mediated mRNA decay; nt: nucleotide; wt: wildtype; TGP: 1000 Genomes Project

MutationT@ster 2025

Variant:

11:57614474C>A_8_ENST00000378323

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Known disease mutation: ClinVar ID 3948 (pathogenic)
Protein features (might be) affected

Model: simple_aae
Tree vote: 95|5 (del | benign) ?
Automatic classification due to ClinVar

Analysed issue

Analysis result

Variant

Chr11:57614474C>A (GRCh38)

Gene symbol

Gene constraints

LOEUF: 0.31, LOF (oe): 0.15, misssense (oe): 0.80, synonymous (oe): 0.90 ? (gnomAD)

Ensembl transcript ID

ENST00000378323.8

Genbank transcript ID

UniProt / AlphaMissense peptide

IC1_HUMAN | AlphaMissense: transcript, gene

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.1411C>A
g.17088C>A

AA changes

AAE:	R471S	?
Score:	110

Frameshift

No

Length of protein

Normal

Pathogenic variant (ClinVar)

Hereditary C1 esterase inhibitor deficiency - dysfunctional factor

pathogenic

Variant DBs

	Not in dbSNP
	Allele 'A' was not found in gnomAD

Protein conservation

Species	Match	AA	Alignment
Human		471	E	A	A	A	A	S	A	I	S	V	A	R	T	L	L	V	F	E	V	Q	Q	P	F	L
mutated	not conserved	471	E	A	A	A	A	S	A	I	S	V	A	S	T	L	L	V	F	E	V	Q	Q
Ptroglodytes	no homologue
Mmulatta	no homologue
Fcatus	no homologue
Mmusculus	no homologue
Ggallus	no homologue
Trubripes	no homologue
Drerio	no homologue
Dmelanogaster	no homologue
Celegans	no homologue
Xtropicalis	no homologue

Protein features

Start (aa)	End (aa)	Feature	Details
23	500	CHAIN		lost
469	472	STRAND		lost

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	0.771	1
	3.231	1
(flanking)	6.208	1

?

Splice sites

No abrogation of potential splice sites predicted by MaxEntScan.

Distance from splice site

N/A

Kozak consensus sequence altered?

No

poly(A) signal

N/A

AA sequence altered

Yes

Chromosome

11

Strand

1

Original gDNA sequence snippet

CCTCCGCCATCTCTGTGGCCCGCACCCTGCTGGTCTTTGAA

Altered gDNA sequence snippet

CCTCCGCCATCTCTGTGGCCAGCACCCTGCTGGTCTTTGAA

Original cDNA sequence snippet

CCTCCGCCATCTCTGTGGCCCGCACCCTGCTGGTCTTTGAA

Altered cDNA sequence snippet

CCTCCGCCATCTCTGTGGCCAGCACCCTGCTGGTCTTTGAA

Wildtype AA sequence

MASRLTLLTL LLLLLAGFLE PQDRASSNPN ATSSSSQDPE SLQDRGEGKV ATTVISKMLF
VEPILEVSSL PTTNSTTNSA TKITANTTDE PTTQPTTEPT TQPTIQPTQP TTQLPTDSPT
QPTTGSFCPG PVTLCSDLES HSTEAVLGDA LVDFSLKLYH AFSAMKKVET NMAFSPFSIA
SLLTQVLLGA GENTKTNLES ILSYPKDFTC VHQALKGFTT KGVTSVSQIF HSPDLAIRDT
FVNASRTLYS SSPRVLSNNS DANLELINTW VAKNTNNKIS RLLDSLPSDT RLVLLNAIYL
SAKWKTTFDP KKTRMEPFHF KNSVIKVPMM NSKKYPVAHF IDQTLKAKVG QLQLSHNLSL
VILVPQNLKH RLEDMEQALS PSVFKAIMEK LEMSKFQPTL LTLPRIKVTT SQDMLSIMEK
LEFFDFSYDL NLCGLTEDPD LQVSAMQHQT VLELTETGVE AAAASAISVA RTLLVFEVQQ
PFLFVLWDQQ HKFPVFMGRV YDPRA*

Mutated AA sequence

MASRLTLLTL LLLLLAGFLE PQDRASSNPN ATSSSSQDPE SLQDRGEGKV ATTVISKMLF
VEPILEVSSL PTTNSTTNSA TKITANTTDE PTTQPTTEPT TQPTIQPTQP TTQLPTDSPT
QPTTGSFCPG PVTLCSDLES HSTEAVLGDA LVDFSLKLYH AFSAMKKVET NMAFSPFSIA
SLLTQVLLGA GENTKTNLES ILSYPKDFTC VHQALKGFTT KGVTSVSQIF HSPDLAIRDT
FVNASRTLYS SSPRVLSNNS DANLELINTW VAKNTNNKIS RLLDSLPSDT RLVLLNAIYL
SAKWKTTFDP KKTRMEPFHF KNSVIKVPMM NSKKYPVAHF IDQTLKAKVG QLQLSHNLSL
VILVPQNLKH RLEDMEQALS PSVFKAIMEK LEMSKFQPTL LTLPRIKVTT SQDMLSIMEK
LEFFDFSYDL NLCGLTEDPD LQVSAMQHQT VLELTETGVE AAAASAISVA STLLVFEVQQ
PFLFVLWDQQ HKFPVFMGRV YDPRA*

Position of stopcodon in wt / mu CDS

1518 / 1518

Position (AA) of stopcodon in wt / mu AA sequence

506 / 506

Position of stopcodon in wt / mu cDNA

1575 / 1575

Position of start ATG in wt / mu cDNA

58 / 58

Last intron/exon boundary

1321

Theoretical NMD boundary in CDS

1213

Length of CDS

1518

Coding sequence (CDS) position

1411

cDNA position

1468

gDNA position

17088

Chromosomal position

57614474

Speed

0.36 s

All positions are in basepairs (bp) if not explicitly stated differently. cDNA/gDNA/chromosomal position: Ins/del are shown as 'last normal base / first normal base'.
AA/aa: amino acid; CDS: coding sequence; mu: mutated; NMD: nonsense-mediated mRNA decay; nt: nucleotide; wt: wildtype; TGP: 1000 Genomes Project

MutationT@ster 2025

Variant:

11:57614474C>A_3_ENST00000278407

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Known disease mutation: ClinVar ID 3948 (pathogenic)
Protein features (might be) affected

Model: simple_aae
Tree vote: 96|4 (del | benign) ?
Automatic classification due to ClinVar

Analysed issue

Analysis result

Variant

Chr11:57614474C>A (GRCh38)

Gene symbol

Gene constraints

LOEUF: 0.28, LOF (oe): 0.13, misssense (oe): 0.80, synonymous (oe): 0.90 ? (gnomAD)

Ensembl transcript ID

ENST00000278407.9

Genbank transcript ID

NM_000062 (exact from MANE), NM_001032295 (by similarity)

UniProt / AlphaMissense peptide

IC1_HUMAN | AlphaMissense: transcript, gene

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.1396C>A
g.17088C>A

AA changes

AAE:	R466S	?
Score:	110

Frameshift

No

Length of protein

Normal

Pathogenic variant (ClinVar)

Hereditary C1 esterase inhibitor deficiency - dysfunctional factor

pathogenic

Variant DBs

	Not in dbSNP
	Allele 'A' was not found in gnomAD

Protein conservation

Species	Match	AA	Alignment
Human		466	E	A	A	A	A	S	A	I	S	V	A	R	T	L	L	V	F	E	V	Q	Q	P	F	L
mutated	not conserved	466	E	A	A	A	A	S	A	I	S	V	A	S	T	L	L	V	F	E	V	Q	Q	P	F
Ptroglodytes	all identical	462	E	A	A	A	A	S	A	I	S	V	A	R	T	L	L	I	F	E	V	Q	Q	P	F
Mmulatta	all identical	593	E	A	A	A	A	S	A	I	S	V	A	R	A	L	L	I	F	E	V	Q	Q	P	F
Fcatus	all identical	478	E	A	A	A	A	S	A	V	S	V	A	R	N	L	L	V	F	E	V	Q	Q	P	F
Mmusculus	all identical	470	E	A	A	A	A	S	A	I	S	F	G	R	S	L	P	I	F	E	V	Q
Ggallus	all identical	486	E	A	A	G	A	M	A	T	S	L	A	R	I	A	L	Q	L	E
Trubripes	no homologue
Drerio	no homologue
Dmelanogaster	no homologue
Celegans	no homologue
Xtropicalis	no homologue

Protein features

Start (aa)	End (aa)	Feature	Details
23	500	CHAIN		lost
465	466	SITE	Reactive bond	lost
466	467	SITE	Reactive bond	lost

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	0.771	1
	3.231	1
(flanking)	6.208	1

?

Splice sites

No abrogation of potential splice sites predicted by MaxEntScan.

Distance from splice site

N/A

Kozak consensus sequence altered?

No

poly(A) signal

N/A

AA sequence altered

Yes

Chromosome

11

Strand

1

Original gDNA sequence snippet

CCTCCGCCATCTCTGTGGCCCGCACCCTGCTGGTCTTTGAA

Altered gDNA sequence snippet

CCTCCGCCATCTCTGTGGCCAGCACCCTGCTGGTCTTTGAA

Original cDNA sequence snippet

CCTCCGCCATCTCTGTGGCCCGCACCCTGCTGGTCTTTGAA

Altered cDNA sequence snippet

CCTCCGCCATCTCTGTGGCCAGCACCCTGCTGGTCTTTGAA

Wildtype AA sequence

MASRLTLLTL LLLLLAGDRA SSNPNATSSS SQDPESLQDR GEGKVATTVI SKMLFVEPIL
EVSSLPTTNS TTNSATKITA NTTDEPTTQP TTEPTTQPTI QPTQPTTQLP TDSPTQPTTG
SFCPGPVTLC SDLESHSTEA VLGDALVDFS LKLYHAFSAM KKVETNMAFS PFSIASLLTQ
VLLGAGENTK TNLESILSYP KDFTCVHQAL KGFTTKGVTS VSQIFHSPDL AIRDTFVNAS
RTLYSSSPRV LSNNSDANLE LINTWVAKNT NNKISRLLDS LPSDTRLVLL NAIYLSAKWK
TTFDPKKTRM EPFHFKNSVI KVPMMNSKKY PVAHFIDQTL KAKVGQLQLS HNLSLVILVP
QNLKHRLEDM EQALSPSVFK AIMEKLEMSK FQPTLLTLPR IKVTTSQDML SIMEKLEFFD
FSYDLNLCGL TEDPDLQVSA MQHQTVLELT ETGVEAAAAS AISVARTLLV FEVQQPFLFV
LWDQQHKFPV FMGRVYDPRA *

Mutated AA sequence

MASRLTLLTL LLLLLAGDRA SSNPNATSSS SQDPESLQDR GEGKVATTVI SKMLFVEPIL
EVSSLPTTNS TTNSATKITA NTTDEPTTQP TTEPTTQPTI QPTQPTTQLP TDSPTQPTTG
SFCPGPVTLC SDLESHSTEA VLGDALVDFS LKLYHAFSAM KKVETNMAFS PFSIASLLTQ
VLLGAGENTK TNLESILSYP KDFTCVHQAL KGFTTKGVTS VSQIFHSPDL AIRDTFVNAS
RTLYSSSPRV LSNNSDANLE LINTWVAKNT NNKISRLLDS LPSDTRLVLL NAIYLSAKWK
TTFDPKKTRM EPFHFKNSVI KVPMMNSKKY PVAHFIDQTL KAKVGQLQLS HNLSLVILVP
QNLKHRLEDM EQALSPSVFK AIMEKLEMSK FQPTLLTLPR IKVTTSQDML SIMEKLEFFD
FSYDLNLCGL TEDPDLQVSA MQHQTVLELT ETGVEAAAAS AISVASTLLV FEVQQPFLFV
LWDQQHKFPV FMGRVYDPRA *

Position of stopcodon in wt / mu CDS

1503 / 1503

Position (AA) of stopcodon in wt / mu AA sequence

501 / 501

Position of stopcodon in wt / mu cDNA

1563 / 1563

Position of start ATG in wt / mu cDNA

61 / 61

Last intron/exon boundary

1309

Theoretical NMD boundary in CDS

1198

Length of CDS

1503

Coding sequence (CDS) position

1396

cDNA position

1456

gDNA position

17088

Chromosomal position

57614474

Speed

0.33 s

All positions are in basepairs (bp) if not explicitly stated differently. cDNA/gDNA/chromosomal position: Ins/del are shown as 'last normal base / first normal base'.
AA/aa: amino acid; CDS: coding sequence; mu: mutated; NMD: nonsense-mediated mRNA decay; nt: nucleotide; wt: wildtype; TGP: 1000 Genomes Project

MutationT@ster 2025

Variant:

11:57614474C>A_1_ENST00000619430

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Known disease mutation: ClinVar ID 3948 (pathogenic)

Model: simple_aae
Tree vote: 97|3 (del | benign) ?
Automatic classification due to ClinVar

Analysed issue

Analysis result

Variant

Chr11:57614474C>A (GRCh38)

Gene symbol

Gene constraints

LOEUF: 0.32, LOF (oe): 0.15, misssense (oe): 0.80, synonymous (oe): 0.93 ? (gnomAD)

Ensembl transcript ID

ENST00000619430.2

Genbank transcript ID

UniProt / AlphaMissense peptide

N/A

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.1192C>A
g.17088C>A

AA changes

AAE:	R398S	?
Score:	110

Frameshift

No

Length of protein

Normal

Pathogenic variant (ClinVar)

Hereditary C1 esterase inhibitor deficiency - dysfunctional factor

pathogenic

Variant DBs

	Not in dbSNP
	Allele 'A' was not found in gnomAD

Protein conservation

Species	Match	AA	Alignment
Human		398	E	A	A	A	A	S	A	I	S	V	A	R	T	L	L	V	F	E	V	Q	Q	P	F	L
mutated	not conserved	398	E	A	A	A	A	S	A	I	S	V	A	S	T	L	L	V	F	E	V	Q	Q	P	F
Ptroglodytes	no homologue
Mmulatta	no homologue
Fcatus	no homologue
Mmusculus	no homologue
Ggallus	no homologue
Trubripes	no homologue
Drerio	no homologue
Dmelanogaster	no homologue
Celegans	no homologue
Xtropicalis	no homologue

Protein features

N/A

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	0.771	1
	3.231	1
(flanking)	6.208	1

?

Splice sites

No abrogation of potential splice sites predicted by MaxEntScan.

Distance from splice site

N/A

Kozak consensus sequence altered?

No

poly(A) signal

N/A

AA sequence altered

Yes

Chromosome

11

Strand

1

Original gDNA sequence snippet

CCTCCGCCATCTCTGTGGCCCGCACCCTGCTGGTCTTTGAA

Altered gDNA sequence snippet

CCTCCGCCATCTCTGTGGCCAGCACCCTGCTGGTCTTTGAA

Original cDNA sequence snippet

CCTCCGCCATCTCTGTGGCCCGCACCCTGCTGGTCTTTGAA

Altered cDNA sequence snippet

CCTCCGCCATCTCTGTGGCCAGCACCCTGCTGGTCTTTGAA

Wildtype AA sequence

MASRLTLLTL LLLLLAGDRA SSNPNATSSS SQDPESLQDR GEGKVATTVI SKMLFVEPIL
EVSSLPTTNS TTNSATKITA NTTDEPTTQP TTEPTTQPTI QPTQPTTQLP TDSPTQPTTG
SFCPGPVTLC SDLESHSTEA VLGDALVDFS LKLYHAFSAM KKVETNMAFS PFSIASLLTQ
VLLGAGENTK TNLESILSYP KDFTCVHQAL KGFTTKGVTS VSQIFHSPAK WKTTFDPKKT
RMEPFHFKNS VIKVPMMNSK KYPVAHFIDQ TLKAKVGQLQ LSHNLSLVIL VPQNLKHRLE
DMEQALSPSV FKAIMEKLEM SKFQPTLLTL PRIKVTTSQD MLSIMEKLEF FDFSYDLNLC
GLTEDPDLQV SAMQHQTVLE LTETGVEAAA ASAISVARTL LVFEVQQPFL FVLWDQQHKF
PVFMGRVYDP RA*

Mutated AA sequence

MASRLTLLTL LLLLLAGDRA SSNPNATSSS SQDPESLQDR GEGKVATTVI SKMLFVEPIL
EVSSLPTTNS TTNSATKITA NTTDEPTTQP TTEPTTQPTI QPTQPTTQLP TDSPTQPTTG
SFCPGPVTLC SDLESHSTEA VLGDALVDFS LKLYHAFSAM KKVETNMAFS PFSIASLLTQ
VLLGAGENTK TNLESILSYP KDFTCVHQAL KGFTTKGVTS VSQIFHSPAK WKTTFDPKKT
RMEPFHFKNS VIKVPMMNSK KYPVAHFIDQ TLKAKVGQLQ LSHNLSLVIL VPQNLKHRLE
DMEQALSPSV FKAIMEKLEM SKFQPTLLTL PRIKVTTSQD MLSIMEKLEF FDFSYDLNLC
GLTEDPDLQV SAMQHQTVLE LTETGVEAAA ASAISVASTL LVFEVQQPFL FVLWDQQHKF
PVFMGRVYDP RA*

Position of stopcodon in wt / mu CDS

1299 / 1299

Position (AA) of stopcodon in wt / mu AA sequence

433 / 433

Position of stopcodon in wt / mu cDNA

1481 / 1481

Position of start ATG in wt / mu cDNA

183 / 183

Last intron/exon boundary

1227

Theoretical NMD boundary in CDS

994

Length of CDS

1299

Coding sequence (CDS) position

1192

cDNA position

1374

gDNA position

17088

Chromosomal position

57614474

Speed

0.36 s

All positions are in basepairs (bp) if not explicitly stated differently. cDNA/gDNA/chromosomal position: Ins/del are shown as 'last normal base / first normal base'.
AA/aa: amino acid; CDS: coding sequence; mu: mutated; NMD: nonsense-mediated mRNA decay; nt: nucleotide; wt: wildtype; TGP: 1000 Genomes Project

MutationT@ster 2025

Variant:

11:57614474C>A_4_ENST00000676670

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Known disease mutation: ClinVar ID 3948 (pathogenic)
Protein features (might be) affected

Model: simple_aae
Tree vote: 98|2 (del | benign) ?
Automatic classification due to ClinVar

Analysed issue

Analysis result

Variant

Chr11:57614474C>A (GRCh38)

Gene symbol

Gene constraints

LOEUF: 0.26, LOF (oe): 0.12, misssense (oe): 0.80, synonymous (oe): 0.90 ? (gnomAD)

Ensembl transcript ID

ENST00000676670.1

Genbank transcript ID

UniProt / AlphaMissense peptide

IC1_HUMAN | AlphaMissense: transcript, gene

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.1396C>A
g.17088C>A

AA changes

AAE:	R466S	?
Score:	110

Frameshift

No

Length of protein

Normal

Pathogenic variant (ClinVar)

Hereditary C1 esterase inhibitor deficiency - dysfunctional factor

pathogenic

Variant DBs

	Not in dbSNP
	Allele 'A' was not found in gnomAD

Protein conservation

Species	Match	AA	Alignment
Human		466	E	A	A	A	A	S	A	I	S	V	A	R	T	L	L	V	F	E	V	Q	Q	P	F	L
mutated	not conserved	466	E	A	A	A	A	S	A	I	S	V	A	S	T	L	L	V	F	E	V	Q	Q	P	F
Ptroglodytes	no homologue
Mmulatta	no homologue
Fcatus	no homologue
Mmusculus	no homologue
Ggallus	no homologue
Trubripes	no homologue
Drerio	no homologue
Dmelanogaster	no homologue
Celegans	no homologue
Xtropicalis	no homologue

Protein features

Start (aa)	End (aa)	Feature	Details
23	500	CHAIN		lost
465	466	SITE	Reactive bond	lost
466	467	SITE	Reactive bond	lost

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	0.771	1
	3.231	1
(flanking)	6.208	1

?

Splice sites

No abrogation of potential splice sites predicted by MaxEntScan.

Distance from splice site

N/A

Kozak consensus sequence altered?

No

poly(A) signal

N/A

AA sequence altered

Yes

Chromosome

11

Strand

1

Original gDNA sequence snippet

CCTCCGCCATCTCTGTGGCCCGCACCCTGCTGGTCTTTGAA

Altered gDNA sequence snippet

CCTCCGCCATCTCTGTGGCCAGCACCCTGCTGGTCTTTGAA

Original cDNA sequence snippet

CCTCCGCCATCTCTGTGGCCCGCACCCTGCTGGTCTTTGAA

Altered cDNA sequence snippet

CCTCCGCCATCTCTGTGGCCAGCACCCTGCTGGTCTTTGAA

Wildtype AA sequence

MASRLTLLTL LLLLLAGDRA SSNPNATSSS SQDPESLQDR GEGKVATTVI SKMLFVEPIL
EVSSLPTTNS TTNSATKITA NTTDEPTTQP TTEPTTQPTI QPTQPTTQLP TDSPTQPTTG
SFCPGPVTLC SDLESHSTEA VLGDALVDFS LKLYHAFSAM KKVETNMAFS PFSIASLLTQ
VLLGAGENTK TNLESILSYP KDFTCVHQAL KGFTTKGVTS VSQIFHSPDL AIRDTFVNAS
RTLYSSSPRV LSNNSDANLE LINTWVAKNT NNKISRLLDS LPSDTRLVLL NAIYLSAKWK
TTFDPKKTRM EPFHFKNSVI KVPMMNSKKY PVAHFIDQTL KAKVGQLQLS HNLSLVILVP
QNLKHRLEDM EQALSPSVFK AIMEKLEMSK FQPTLLTLPR IKVTTSQDML SIMEKLEFFD
FSYDLNLCGL TEDPDLQVSA MQHQTVLELT ETGVEAAAAS AISVARTLLV FEVQQPFLFV
LWDQQHKFPV FMGRVYDPRA *

Mutated AA sequence

MASRLTLLTL LLLLLAGDRA SSNPNATSSS SQDPESLQDR GEGKVATTVI SKMLFVEPIL
EVSSLPTTNS TTNSATKITA NTTDEPTTQP TTEPTTQPTI QPTQPTTQLP TDSPTQPTTG
SFCPGPVTLC SDLESHSTEA VLGDALVDFS LKLYHAFSAM KKVETNMAFS PFSIASLLTQ
VLLGAGENTK TNLESILSYP KDFTCVHQAL KGFTTKGVTS VSQIFHSPDL AIRDTFVNAS
RTLYSSSPRV LSNNSDANLE LINTWVAKNT NNKISRLLDS LPSDTRLVLL NAIYLSAKWK
TTFDPKKTRM EPFHFKNSVI KVPMMNSKKY PVAHFIDQTL KAKVGQLQLS HNLSLVILVP
QNLKHRLEDM EQALSPSVFK AIMEKLEMSK FQPTLLTLPR IKVTTSQDML SIMEKLEFFD
FSYDLNLCGL TEDPDLQVSA MQHQTVLELT ETGVEAAAAS AISVASTLLV FEVQQPFLFV
LWDQQHKFPV FMGRVYDPRA *

Position of stopcodon in wt / mu CDS

1503 / 1503

Position (AA) of stopcodon in wt / mu AA sequence

501 / 501

Position of stopcodon in wt / mu cDNA

1590 / 1590

Position of start ATG in wt / mu cDNA

88 / 88

Last intron/exon boundary

1605

Theoretical NMD boundary in CDS

1467

Length of CDS

1503

Coding sequence (CDS) position

1396

cDNA position

1483

gDNA position

17088

Chromosomal position

57614474

Speed

0.32 s

All positions are in basepairs (bp) if not explicitly stated differently. cDNA/gDNA/chromosomal position: Ins/del are shown as 'last normal base / first normal base'.
AA/aa: amino acid; CDS: coding sequence; mu: mutated; NMD: nonsense-mediated mRNA decay; nt: nucleotide; wt: wildtype; TGP: 1000 Genomes Project

MutationT@ster 2025

Variant:

11:57614474C>A_6_ENST00000403558

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Known disease mutation: ClinVar ID 3948 (pathogenic)

Model: simple_aae
Tree vote: 99|1 (del | benign) ?
Automatic classification due to ClinVar

Analysed issue

Analysis result

Variant

Chr11:57614474C>A (GRCh38)

Gene symbol

Gene constraints

LOEUF: 0.27, LOF (oe): 0.12, misssense (oe): 0.82, synonymous (oe): 0.93 ? (gnomAD)

Ensembl transcript ID

ENST00000403558.1

Genbank transcript ID

UniProt / AlphaMissense peptide

N/A

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.1525C>A
g.17088C>A

AA changes

AAE:	R509S	?
Score:	110

Frameshift

No

Length of protein

Normal

Pathogenic variant (ClinVar)

Hereditary C1 esterase inhibitor deficiency - dysfunctional factor

pathogenic

Variant DBs

	Not in dbSNP
	Allele 'A' was not found in gnomAD

Protein conservation

Species	Match	AA	Alignment
Human		509	E	A	A	A	A	S	A	I	S	V	A	R	T	L	L	V	F	E	V	Q	Q	P	F	L
mutated	not conserved	509	E	A	A	A	A	S	A	I	S	V	A	S	T	L	L	V	F	E	V	Q	Q	P	F
Ptroglodytes	no homologue
Mmulatta	no homologue
Fcatus	no homologue
Mmusculus	no homologue
Ggallus	no homologue
Trubripes	no homologue
Drerio	no homologue
Dmelanogaster	no homologue
Celegans	no homologue
Xtropicalis	no homologue

Protein features

N/A

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	0.771	1
	3.231	1
(flanking)	6.208	1

?

Splice sites

No abrogation of potential splice sites predicted by MaxEntScan.

Distance from splice site

N/A

Kozak consensus sequence altered?

No

poly(A) signal

N/A

AA sequence altered

Yes

Chromosome

11

Strand

1

Original gDNA sequence snippet

CCTCCGCCATCTCTGTGGCCCGCACCCTGCTGGTCTTTGAA

Altered gDNA sequence snippet

CCTCCGCCATCTCTGTGGCCAGCACCCTGCTGGTCTTTGAA

Original cDNA sequence snippet

CCTCCGCCATCTCTGTGGCCCGCACCCTGCTGGTCTTTGAA

Altered cDNA sequence snippet

CCTCCGCCATCTCTGTGGCCAGCACCCTGCTGGTCTTTGAA

Wildtype AA sequence

MGAGPGRGGG PWAPRVGAGS EAGWLRRSAD VAAQMASRLT LLTLLLLLLA GDRASSNPNA
TSSSSQDPES LQDRGEGKVA TTVISKMLFV EPILEVSSLP TTNSTTNSAT KITANTTDEP
TTQPTTEPTT QPTIQPTQPT TQLPTDSPTQ PTTGSFCPGP VTLCSDLESH STEAVLGDAL
VDFSLKLYHA FSAMKKVETN MAFSPFSIAS LLTQVLLGAG ENTKTNLESI LSYPKDFTCV
HQALKGFTTK GVTSVSQIFH SPDLAIRDTF VNASRTLYSS SPRVLSNNSD ANLELINTWV
AKNTNNKISR LLDSLPSDTR LVLLNAIYLS EQPSHLFPLA KWKTTFDPKK TRMEPFHFKN
SVIKVPMMNS KKYPVAHFID QTLKAKVGQL QLSHNLSLVI LVPQNLKHRL EDMEQALSPS
VFKAIMEKLE MSKFQPTLLT LPRIKVTTSQ DMLSIMEKLE FFDFSYDLNL CGLTEDPDLQ
VSAMQHQTVL ELTETGVEAA AASAISVART LLVFEVQQPF LFVLWDQQHK FPVFMGRVYD
PRA*

Mutated AA sequence

MGAGPGRGGG PWAPRVGAGS EAGWLRRSAD VAAQMASRLT LLTLLLLLLA GDRASSNPNA
TSSSSQDPES LQDRGEGKVA TTVISKMLFV EPILEVSSLP TTNSTTNSAT KITANTTDEP
TTQPTTEPTT QPTIQPTQPT TQLPTDSPTQ PTTGSFCPGP VTLCSDLESH STEAVLGDAL
VDFSLKLYHA FSAMKKVETN MAFSPFSIAS LLTQVLLGAG ENTKTNLESI LSYPKDFTCV
HQALKGFTTK GVTSVSQIFH SPDLAIRDTF VNASRTLYSS SPRVLSNNSD ANLELINTWV
AKNTNNKISR LLDSLPSDTR LVLLNAIYLS EQPSHLFPLA KWKTTFDPKK TRMEPFHFKN
SVIKVPMMNS KKYPVAHFID QTLKAKVGQL QLSHNLSLVI LVPQNLKHRL EDMEQALSPS
VFKAIMEKLE MSKFQPTLLT LPRIKVTTSQ DMLSIMEKLE FFDFSYDLNL CGLTEDPDLQ
VSAMQHQTVL ELTETGVEAA AASAISVAST LLVFEVQQPF LFVLWDQQHK FPVFMGRVYD
PRA*

Position of stopcodon in wt / mu CDS

1632 / 1632

Position (AA) of stopcodon in wt / mu AA sequence

544 / 544

Position of stopcodon in wt / mu cDNA

1998 / 1998

Position of start ATG in wt / mu cDNA

367 / 367

Last intron/exon boundary

1744

Theoretical NMD boundary in CDS

1327

Length of CDS

1632

Coding sequence (CDS) position

1525

cDNA position

1891

gDNA position

17088

Chromosomal position

57614474

Speed

0.35 s

All positions are in basepairs (bp) if not explicitly stated differently. cDNA/gDNA/chromosomal position: Ins/del are shown as 'last normal base / first normal base'.
AA/aa: amino acid; CDS: coding sequence; mu: mutated; NMD: nonsense-mediated mRNA decay; nt: nucleotide; wt: wildtype; TGP: 1000 Genomes Project

MutationT@ster 2025

Variant:

11:57614474C>A_2_ENST00000340687

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Known disease mutation: ClinVar ID 3948 (pathogenic)

Model: simple_aae
Tree vote: 100|0 (del | benign) ?
Automatic classification due to ClinVar

Analysed issue

Analysis result

Variant

Chr11:57614474C>A (GRCh38)

Gene symbol

Gene constraints

LOEUF: 0.26, LOF (oe): 0.11, misssense (oe): 0.80, synonymous (oe): 0.93 ? (gnomAD)

Ensembl transcript ID

ENST00000340687.10

Genbank transcript ID

UniProt / AlphaMissense peptide

N/A

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.1285C>A
g.17088C>A

AA changes

AAE:	R429S	?
Score:	110

Frameshift

No

Length of protein

Normal

Pathogenic variant (ClinVar)

Hereditary C1 esterase inhibitor deficiency - dysfunctional factor

pathogenic

Variant DBs

	Not in dbSNP
	Allele 'A' was not found in gnomAD

Protein conservation

Species	Match	AA	Alignment
Human		429	E	A	A	A	A	S	A	I	S	V	A	R	T	L	L	V	F	E	V	Q	Q	P	F	L
mutated	not conserved	429				A	A	S	A	I	S	V	A	S	T	L	L	V	F	E	V	Q	Q	P	F
Ptroglodytes	no homologue
Mmulatta	no homologue
Fcatus	no homologue
Mmusculus	no homologue
Ggallus	no homologue
Trubripes	no homologue
Drerio	no homologue
Dmelanogaster	no homologue
Celegans	no homologue
Xtropicalis	no homologue

Protein features

N/A

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	0.771	1
	3.231	1
(flanking)	6.208	1

?

Splice sites

No abrogation of potential splice sites predicted by MaxEntScan.

Distance from splice site

N/A

Kozak consensus sequence altered?

No

poly(A) signal

N/A

AA sequence altered

Yes

Chromosome

11

Strand

1

Original gDNA sequence snippet

CCTCCGCCATCTCTGTGGCCCGCACCCTGCTGGTCTTTGAA

Altered gDNA sequence snippet

CCTCCGCCATCTCTGTGGCCAGCACCCTGCTGGTCTTTGAA

Original cDNA sequence snippet

CCTCCGCCATCTCTGTGGCCCGCACCCTGCTGGTCTTTGAA

Altered cDNA sequence snippet

CCTCCGCCATCTCTGTGGCCAGCACCCTGCTGGTCTTTGAA

Wildtype AA sequence

MASRLTLLTL LLLLLAGDRA SSNPNATSSS SQDPESLQDR GEGKVATTVI SKMLFVEPIL
EVSSLPTTNS TTNSATKITA NTTDEPTTQP TTEPTTQPTI QPTQPTTQLP TDSPTQPTTG
SFCPGPVTLC SDLESHSTEA VLGDALVDFS LKLYHAFSAM KKVETNMAFS PFSIASLLTQ
VLLGAGENTK TNLESILSYP KDFTCVHQAL KGFTTKGVTS VSQIFHSPDL AIRDTFVNAS
RTLYSSSPRV LSNNSDANLE LINTWVAKNT NNKISRLLDS LPSDTRLVLL NAIYLSAKWK
TTFDPKKTRM EPFHFKNSVI KVPMMNSKKY PVAHFIDQTL KAKAIMEKLE MSKFQPTLLT
LPRIKVTTSQ DMLSIMEKLE FFDFSYDLNL CGLTEDPDLQ VSAMQHQTVL ELTETGVEAA
AASAISVART LLVFEVQQPF LFVLWDQQHK FPVFMGRVYD PRA*

Mutated AA sequence

MASRLTLLTL LLLLLAGDRA SSNPNATSSS SQDPESLQDR GEGKVATTVI SKMLFVEPIL
EVSSLPTTNS TTNSATKITA NTTDEPTTQP TTEPTTQPTI QPTQPTTQLP TDSPTQPTTG
SFCPGPVTLC SDLESHSTEA VLGDALVDFS LKLYHAFSAM KKVETNMAFS PFSIASLLTQ
VLLGAGENTK TNLESILSYP KDFTCVHQAL KGFTTKGVTS VSQIFHSPDL AIRDTFVNAS
RTLYSSSPRV LSNNSDANLE LINTWVAKNT NNKISRLLDS LPSDTRLVLL NAIYLSAKWK
TTFDPKKTRM EPFHFKNSVI KVPMMNSKKY PVAHFIDQTL KAKAIMEKLE MSKFQPTLLT
LPRIKVTTSQ DMLSIMEKLE FFDFSYDLNL CGLTEDPDLQ VSAMQHQTVL ELTETGVEAA
AASAISVAST LLVFEVQQPF LFVLWDQQHK FPVFMGRVYD PRA*

Position of stopcodon in wt / mu CDS

1392 / 1392

Position (AA) of stopcodon in wt / mu AA sequence

464 / 464

Position of stopcodon in wt / mu cDNA

1454 / 1454

Position of start ATG in wt / mu cDNA

63 / 63

Last intron/exon boundary

1200

Theoretical NMD boundary in CDS

1087

Length of CDS

1392

Coding sequence (CDS) position

1285

cDNA position

1347

gDNA position

17088

Chromosomal position

57614474

Speed

0.34 s

All positions are in basepairs (bp) if not explicitly stated differently. cDNA/gDNA/chromosomal position: Ins/del are shown as 'last normal base / first normal base'.
AA/aa: amino acid; CDS: coding sequence; mu: mutated; NMD: nonsense-mediated mRNA decay; nt: nucleotide; wt: wildtype; TGP: 1000 Genomes Project

MutationT@ster 2025

Variant:

11:57614474C>A_5_ENST00000677625

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Known disease mutation: ClinVar ID 3948 (pathogenic)

Model: simple_aae
Tree vote: 100|0 (del | benign) ?
Automatic classification due to ClinVar

Analysed issue

Analysis result

Variant

Chr11:57614474C>A (GRCh38)

Gene symbol

Gene constraints

LOEUF: 0.25, LOF (oe): 0.11, misssense (oe): 0.80, synonymous (oe): 0.92 ? (gnomAD)

Ensembl transcript ID

ENST00000677625.1

Genbank transcript ID

UniProt / AlphaMissense peptide

N/A

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.1342C>A
g.17088C>A

AA changes

AAE:	R448S	?
Score:	110

Frameshift

No

Length of protein

Normal

Pathogenic variant (ClinVar)

Hereditary C1 esterase inhibitor deficiency - dysfunctional factor

pathogenic

Variant DBs

	Not in dbSNP
	Allele 'A' was not found in gnomAD

Protein conservation

Species	Match	AA	Alignment
Human		448	E	A	A	A	A	S	A	I	S	V	A	R	T	L	L	V	F	E	V	Q	Q	P	F	L
mutated	not conserved	448	E	A	A	A	A	S	A	I	S	V	A	S	T	L	L	V	F	E	V	Q	Q	P	F
Ptroglodytes	no homologue
Mmulatta	no homologue
Fcatus	no homologue
Mmusculus	no homologue
Ggallus	no homologue
Trubripes	no homologue
Drerio	no homologue
Dmelanogaster	no homologue
Celegans	no homologue
Xtropicalis	no homologue

Protein features

N/A

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	0.771	1
	3.231	1
(flanking)	6.208	1

?

Splice sites

No abrogation of potential splice sites predicted by MaxEntScan.

Distance from splice site

N/A

Kozak consensus sequence altered?

No

poly(A) signal

N/A

AA sequence altered

Yes

Chromosome

11

Strand

1

Original gDNA sequence snippet

CCTCCGCCATCTCTGTGGCCCGCACCCTGCTGGTCTTTGAA

Altered gDNA sequence snippet

CCTCCGCCATCTCTGTGGCCAGCACCCTGCTGGTCTTTGAA

Original cDNA sequence snippet

CCTCCGCCATCTCTGTGGCCCGCACCCTGCTGGTCTTTGAA

Altered cDNA sequence snippet

CCTCCGCCATCTCTGTGGCCAGCACCCTGCTGGTCTTTGAA

Wildtype AA sequence

MASRLTLLTL LLLLLAGDRA SSNPNATSSS SQDPESLQDR GEGKVATTVI SKMLFVEPIL
EVSSLPTTNS TTNSATKITA NTTDEPTTQP TTEPTTQPTI QPTQPTTQLP TDSPTQPTTG
SFCPGPVTLC SDLESHSTEA VLGDALVDFS LKLYHAFSAM KKVETNMAFS PFSIASLLTQ
VLLGAGENTK TNLESILSYP KDFTCVHQAL KGFTTKGVTS VSQIFHSPDL AIRDTFVNAS
RTLYSSSPRV LSNNSDANLE LINTWVAKNT NNKISRLLDS LPSDTRLVLL NAIYLSAKWK
TTFDPKKTRM EPFHFKNSVI KVPMMNSKKY PVAHFIDQTL KAKNLKHRLE DMEQALSPSV
FKAIMEKLEM SKFQPTLLTL PRIKVTTSQD MLSIMEKLEF FDFSYDLNLC GLTEDPDLQV
SAMQHQTVLE LTETGVEAAA ASAISVARTL LVFEVQQPFL FVLWDQQHKF PVFMGRVYDP
RA*

Mutated AA sequence

MASRLTLLTL LLLLLAGDRA SSNPNATSSS SQDPESLQDR GEGKVATTVI SKMLFVEPIL
EVSSLPTTNS TTNSATKITA NTTDEPTTQP TTEPTTQPTI QPTQPTTQLP TDSPTQPTTG
SFCPGPVTLC SDLESHSTEA VLGDALVDFS LKLYHAFSAM KKVETNMAFS PFSIASLLTQ
VLLGAGENTK TNLESILSYP KDFTCVHQAL KGFTTKGVTS VSQIFHSPDL AIRDTFVNAS
RTLYSSSPRV LSNNSDANLE LINTWVAKNT NNKISRLLDS LPSDTRLVLL NAIYLSAKWK
TTFDPKKTRM EPFHFKNSVI KVPMMNSKKY PVAHFIDQTL KAKNLKHRLE DMEQALSPSV
FKAIMEKLEM SKFQPTLLTL PRIKVTTSQD MLSIMEKLEF FDFSYDLNLC GLTEDPDLQV
SAMQHQTVLE LTETGVEAAA ASAISVASTL LVFEVQQPFL FVLWDQQHKF PVFMGRVYDP
RA*

Position of stopcodon in wt / mu CDS

1449 / 1449

Position (AA) of stopcodon in wt / mu AA sequence

483 / 483

Position of stopcodon in wt / mu cDNA

1536 / 1536

Position of start ATG in wt / mu cDNA

88 / 88

Last intron/exon boundary

1282

Theoretical NMD boundary in CDS

1144

Length of CDS

1449

Coding sequence (CDS) position

1342

cDNA position

1429

gDNA position

17088

Chromosomal position

57614474

Speed

0.31 s

All positions are in basepairs (bp) if not explicitly stated differently. cDNA/gDNA/chromosomal position: Ins/del are shown as 'last normal base / first normal base'.
AA/aa: amino acid; CDS: coding sequence; mu: mutated; NMD: nonsense-mediated mRNA decay; nt: nucleotide; wt: wildtype; TGP: 1000 Genomes Project