MutationT @ ster 2025

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Known disease mutation: ClinVar ID 464754 (pathogenic)
Protein features (might be) affected

Model: simple_aae
Tree vote: 92|8 (del | benign) ?
Automatic classification due to ClinVar

Analysed issue

Analysis result

Variant

Chr12:51916113A>G (GRCh38)

Gene symbol

Gene constraints

LOEUF: 1.89, LOF (oe): 1.30, misssense (oe): 0.92, synonymous (oe): 1.17 ? (gnomAD)

Ensembl transcript ID

ENST00000551576.6

Genbank transcript ID

NM_001406487 (by similarity)

UniProt / AlphaMissense peptide

ACVL1_HUMAN | AlphaMissense: transcript, gene

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.1126A>G
g.9206A>G

AA changes

AAE:	M376V	?
Score:	21

Frameshift

No

Length of protein

Normal

Pathogenic variant (ClinVar)

Cardiovascular phenotype
Telangiectasia, hereditary hemorrhagic, type 2

pathogenic

Variant DBs

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

Protein conservation

Species	Match	AA	Alignment
Human		376	G	N	N	P	R	V	G	T	K	R	Y	M	A	P	E	V	L	D	E	Q	I	R	T	D
mutated	all conserved	376	G	N	N	P	R	V	G	T	K	R	Y	V	A	P	E	V	L	D	E	Q	I	R	T
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
22	503	CHAIN		lost
142	503	TOPO_DOM	Cytoplasmic	lost
202	492	DOMAIN	Protein kinase	lost

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	7.899	1
	9.317	1
(flanking)	8.01	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

12

Strand

1

Original gDNA sequence snippet

GAGTGGGCACCAAGCGGTACATGGCACCCGAGGTGCTGGAC

Altered gDNA sequence snippet

GAGTGGGCACCAAGCGGTACGTGGCACCCGAGGTGCTGGAC

Original cDNA sequence snippet

GAGTGGGCACCAAGCGGTACATGGCACCCGAGGTGCTGGAC

Altered cDNA sequence snippet

GAGTGGGCACCAAGCGGTACGTGGCACCCGAGGTGCTGGAC

Wildtype AA sequence

MTLGSPRKGL LMLLMALVTQ GDPVKPSRGP LVTCTCESPH CKGPTCRGAW CTVVLVREEG
RHPQEHRGCG NLHRELCRGR PTEFVNHYCC DSHLCNHNVS LVLEATQPPS EQPGTDGQLA
LILGPVLALL ALVALGVLGL WHVRRRQEKQ RGLHSELGES SLILKASEQG DSMLGDLLDS
DCTTGSGSGL PFLVQRTVAR QVALVECVGK GRYGEVWRGL WHGESVAVKI FSSRDEQSWF
RETEIYNTVL LRHDNILGFI ASDMTSRNSS TQLWLITHYH EHGSLYDFLQ RQTLEPHLAL
RLAVSAACGL AHLHVEIFGT QGKPAIAHRD FKSRNVLVKS NLQCCIADLG LAVMHSQGSD
YLDIGNNPRV GTKRYMAPEV LDEQIRTDCF ESYKWTDIWA FGLVLWEIAR RTIVNGIVED
YRPPFYDVVP NDPSFEDMKK VVCVDQQTPT IPNRLAADPV LSGLAQMMRE CWYPNPSARL
TALRIKKTLQ KISNSPEKPK VIQ*

Mutated AA sequence

MTLGSPRKGL LMLLMALVTQ GDPVKPSRGP LVTCTCESPH CKGPTCRGAW CTVVLVREEG
RHPQEHRGCG NLHRELCRGR PTEFVNHYCC DSHLCNHNVS LVLEATQPPS EQPGTDGQLA
LILGPVLALL ALVALGVLGL WHVRRRQEKQ RGLHSELGES SLILKASEQG DSMLGDLLDS
DCTTGSGSGL PFLVQRTVAR QVALVECVGK GRYGEVWRGL WHGESVAVKI FSSRDEQSWF
RETEIYNTVL LRHDNILGFI ASDMTSRNSS TQLWLITHYH EHGSLYDFLQ RQTLEPHLAL
RLAVSAACGL AHLHVEIFGT QGKPAIAHRD FKSRNVLVKS NLQCCIADLG LAVMHSQGSD
YLDIGNNPRV GTKRYVAPEV LDEQIRTDCF ESYKWTDIWA FGLVLWEIAR RTIVNGIVED
YRPPFYDVVP NDPSFEDMKK VVCVDQQTPT IPNRLAADPV LSGLAQMMRE CWYPNPSARL
TALRIKKTLQ KISNSPEKPK VIQ*

Position of stopcodon in wt / mu CDS

1512 / 1512

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

504 / 504

Position of stopcodon in wt / mu cDNA

1802 / 1802

Position of start ATG in wt / mu cDNA

291 / 291

Last intron/exon boundary

1667

Theoretical NMD boundary in CDS

1326

Length of CDS

1512

Coding sequence (CDS) position

1126

cDNA position

1416

gDNA position

9206

Chromosomal position

51916113

Speed

0.04 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:

12:51916113A>G_5_ENST00000388922

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Known disease mutation: ClinVar ID 464754 (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

Chr12:51916113A>G (GRCh38)

Gene symbol

Gene constraints

LOEUF: 0.57, LOF (oe): 0.40, misssense (oe): 0.66, synonymous (oe): 1.02 ? (gnomAD)

Ensembl transcript ID

ENST00000388922.9

Genbank transcript ID

NM_000020 (exact from MANE), NM_001077401 (by similarity)

UniProt / AlphaMissense peptide

ACVL1_HUMAN | AlphaMissense: transcript, gene

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.1126A>G
g.9206A>G

AA changes

AAE:	M376V	?
Score:	21

Frameshift

No

Length of protein

Normal

Pathogenic variant (ClinVar)

Cardiovascular phenotype
Telangiectasia, hereditary hemorrhagic, type 2

pathogenic

Variant DBs

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

Protein conservation

Species	Match	AA	Alignment
Human		376	G	N	N	P	R	V	G	T	K	R	Y	M	A	P	E	V	L	D	E	Q	I	R	T	D
mutated	all conserved	376	G	N	N	P	R	V	G	T	K	R	Y	V	A	P	E	V	L	D	E	Q	I	R	T
Ptroglodytes	all identical	376	G	N	N	P	R	V	G	T	K	R	Y	M	A	P	E	V	L	D	E	Q	I	R	T
Mmulatta	all identical	376	G	N	N	P	R	V	G	T	K	R	Y	M	A	P	E	V	L	D	E	Q	I	R	T
Fcatus	all identical	390	G	N	N	P	R	V	G	T	K	R	Y	M	A	P	E	V	L	E	E	Q	I	R	T
Mmusculus	all identical	375	G	N	N	P	R	V	G	T	K	R	Y	M	A	P	E	V	L	D	E	H	I	R	T
Ggallus	all identical	783	G	H	N	P	R	V	G	T	K	R	Y	M	A	P	E	V	L	S	E	Q	I	R	T
Trubripes	all identical	560	G	N	N	P	K	V	G	T	K	R	Y	M	A	P	E	V	L	D	D	S	I	Q	M
Drerio	no homologue
Dmelanogaster	all identical	450	G	N	N	P	K	V	G	T	K	R	Y	M	A	P	E	V	L	D	E	S	I	D	L
Celegans	all identical	487	L	G	-	-	Q	V	G	T	K	R	Y	M	S	P	E	M	L	-	E	G	A	T	E
Xtropicalis	all identical	378	G	N	N	P	R	V	G	T	K	R	Y	M	A	P	E	V	L	D	E	T	I	R

Protein features

Start (aa)	End (aa)	Feature	Details
22	503	CHAIN		lost
142	503	TOPO_DOM	Cytoplasmic	lost
202	492	DOMAIN	Protein kinase	lost

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	7.899	1
	9.317	1
(flanking)	8.01	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

12

Strand

1

Original gDNA sequence snippet

GAGTGGGCACCAAGCGGTACATGGCACCCGAGGTGCTGGAC

Altered gDNA sequence snippet

GAGTGGGCACCAAGCGGTACGTGGCACCCGAGGTGCTGGAC

Original cDNA sequence snippet

GAGTGGGCACCAAGCGGTACATGGCACCCGAGGTGCTGGAC

Altered cDNA sequence snippet

GAGTGGGCACCAAGCGGTACGTGGCACCCGAGGTGCTGGAC

Wildtype AA sequence

MTLGSPRKGL LMLLMALVTQ GDPVKPSRGP LVTCTCESPH CKGPTCRGAW CTVVLVREEG
RHPQEHRGCG NLHRELCRGR PTEFVNHYCC DSHLCNHNVS LVLEATQPPS EQPGTDGQLA
LILGPVLALL ALVALGVLGL WHVRRRQEKQ RGLHSELGES SLILKASEQG DSMLGDLLDS
DCTTGSGSGL PFLVQRTVAR QVALVECVGK GRYGEVWRGL WHGESVAVKI FSSRDEQSWF
RETEIYNTVL LRHDNILGFI ASDMTSRNSS TQLWLITHYH EHGSLYDFLQ RQTLEPHLAL
RLAVSAACGL AHLHVEIFGT QGKPAIAHRD FKSRNVLVKS NLQCCIADLG LAVMHSQGSD
YLDIGNNPRV GTKRYMAPEV LDEQIRTDCF ESYKWTDIWA FGLVLWEIAR RTIVNGIVED
YRPPFYDVVP NDPSFEDMKK VVCVDQQTPT IPNRLAADPV LSGLAQMMRE CWYPNPSARL
TALRIKKTLQ KISNSPEKPK VIQ*

Mutated AA sequence

MTLGSPRKGL LMLLMALVTQ GDPVKPSRGP LVTCTCESPH CKGPTCRGAW CTVVLVREEG
RHPQEHRGCG NLHRELCRGR PTEFVNHYCC DSHLCNHNVS LVLEATQPPS EQPGTDGQLA
LILGPVLALL ALVALGVLGL WHVRRRQEKQ RGLHSELGES SLILKASEQG DSMLGDLLDS
DCTTGSGSGL PFLVQRTVAR QVALVECVGK GRYGEVWRGL WHGESVAVKI FSSRDEQSWF
RETEIYNTVL LRHDNILGFI ASDMTSRNSS TQLWLITHYH EHGSLYDFLQ RQTLEPHLAL
RLAVSAACGL AHLHVEIFGT QGKPAIAHRD FKSRNVLVKS NLQCCIADLG LAVMHSQGSD
YLDIGNNPRV GTKRYVAPEV LDEQIRTDCF ESYKWTDIWA FGLVLWEIAR RTIVNGIVED
YRPPFYDVVP NDPSFEDMKK VVCVDQQTPT IPNRLAADPV LSGLAQMMRE CWYPNPSARL
TALRIKKTLQ KISNSPEKPK VIQ*

Position of stopcodon in wt / mu CDS

1512 / 1512

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

504 / 504

Position of stopcodon in wt / mu cDNA

1709 / 1709

Position of start ATG in wt / mu cDNA

198 / 198

Last intron/exon boundary

1574

Theoretical NMD boundary in CDS

1326

Length of CDS

1512

Coding sequence (CDS) position

1126

cDNA position

1323

gDNA position

9206

Chromosomal position

51916113

Speed

0.04 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:

12:51916113A>G_3_ENST00000550683

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Known disease mutation: ClinVar ID 464754 (pathogenic)

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

Analysed issue

Analysis result

Variant

Chr12:51916113A>G (GRCh38)

Gene symbol

Gene constraints

LOEUF: 0.57, LOF (oe): 0.39, misssense (oe): 0.67, synonymous (oe): 1.02 ? (gnomAD)

Ensembl transcript ID

ENST00000550683.5

Genbank transcript ID

UniProt / AlphaMissense peptide

N/A

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.1168A>G
g.9206A>G

AA changes

AAE:	M390V	?
Score:	21

Frameshift

No

Length of protein

Normal

Pathogenic variant (ClinVar)

Cardiovascular phenotype
Telangiectasia, hereditary hemorrhagic, type 2

pathogenic

Variant DBs

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

Protein conservation

Species	Match	AA	Alignment
Human		390	G	N	N	P	R	V	G	T	K	R	Y	M	A	P	E	V	L	D	E	Q	I	R	T	D
mutated	all conserved	390	G	N	N	P	R	V	G	T	K	R	Y	V	A	P	E	V	L	D	E	Q	I	R	T
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)	7.899	1
	9.317	1
(flanking)	8.01	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

12

Strand

1

Original gDNA sequence snippet

GAGTGGGCACCAAGCGGTACATGGCACCCGAGGTGCTGGAC

Altered gDNA sequence snippet

GAGTGGGCACCAAGCGGTACGTGGCACCCGAGGTGCTGGAC

Original cDNA sequence snippet

GAGTGGGCACCAAGCGGTACATGGCACCCGAGGTGCTGGAC

Altered cDNA sequence snippet

GAGTGGGCACCAAGCGGTACGTGGCACCCGAGGTGCTGGAC

Wildtype AA sequence

MALTPPLLLL SAGTMTLGSP RKGLLMLLMA LVTQGDPVKP SRGPLVTCTC ESPHCKGPTC
RGAWCTVVLV REEGRHPQEH RGCGNLHREL CRGRPTEFVN HYCCDSHLCN HNVSLVLEAT
QPPSEQPGTD GQLALILGPV LALLALVALG VLGLWHVRRR QEKQRGLHSE LGESSLILKA
SEQGDSMLGD LLDSDCTTGS GSGLPFLVQR TVARQVALVE CVGKGRYGEV WRGLWHGESV
AVKIFSSRDE QSWFRETEIY NTVLLRHDNI LGFIASDMTS RNSSTQLWLI THYHEHGSLY
DFLQRQTLEP HLALRLAVSA ACGLAHLHVE IFGTQGKPAI AHRDFKSRNV LVKSNLQCCI
ADLGLAVMHS QGSDYLDIGN NPRVGTKRYM APEVLDEQIR TDCFESYKWT DIWAFGLVLW
EIARRTIVNG IVEDYRPPFY DVVPNDPSFE DMKKVVCVDQ QTPTIPNRLA ADPVLSGLAQ
MMRECWYPNP SARLTALRIK KTLQKISNSP EKPKVIQ*

Mutated AA sequence

MALTPPLLLL SAGTMTLGSP RKGLLMLLMA LVTQGDPVKP SRGPLVTCTC ESPHCKGPTC
RGAWCTVVLV REEGRHPQEH RGCGNLHREL CRGRPTEFVN HYCCDSHLCN HNVSLVLEAT
QPPSEQPGTD GQLALILGPV LALLALVALG VLGLWHVRRR QEKQRGLHSE LGESSLILKA
SEQGDSMLGD LLDSDCTTGS GSGLPFLVQR TVARQVALVE CVGKGRYGEV WRGLWHGESV
AVKIFSSRDE QSWFRETEIY NTVLLRHDNI LGFIASDMTS RNSSTQLWLI THYHEHGSLY
DFLQRQTLEP HLALRLAVSA ACGLAHLHVE IFGTQGKPAI AHRDFKSRNV LVKSNLQCCI
ADLGLAVMHS QGSDYLDIGN NPRVGTKRYV APEVLDEQIR TDCFESYKWT DIWAFGLVLW
EIARRTIVNG IVEDYRPPFY DVVPNDPSFE DMKKVVCVDQ QTPTIPNRLA ADPVLSGLAQ
MMRECWYPNP SARLTALRIK KTLQKISNSP EKPKVIQ*

Position of stopcodon in wt / mu CDS

1554 / 1554

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

518 / 518

Position of stopcodon in wt / mu cDNA

1655 / 1655

Position of start ATG in wt / mu cDNA

102 / 102

Last intron/exon boundary

1520

Theoretical NMD boundary in CDS

1368

Length of CDS

1554

Coding sequence (CDS) position

1168

cDNA position

1269

gDNA position

9206

Chromosomal position

51916113

Speed

0.04 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:

12:51916113A>G_2_ENST00000419526

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Known disease mutation: ClinVar ID 464754 (pathogenic)

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

Analysed issue

Analysis result

Variant

Chr12:51916113A>G (GRCh38)

Gene symbol

Gene constraints

LOEUF: 0.46, LOF (oe): 0.27, misssense (oe): 0.57, synonymous (oe): 0.96 ? (gnomAD)

Ensembl transcript ID

ENST00000419526.6

Genbank transcript ID

NM_001406495 (by similarity)

UniProt / AlphaMissense peptide

N/A

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.604A>G
g.9206A>G

AA changes

AAE:	M202V	?
Score:	21

Frameshift

No

Length of protein

Normal

Pathogenic variant (ClinVar)

Cardiovascular phenotype
Telangiectasia, hereditary hemorrhagic, type 2

pathogenic

Variant DBs

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

Protein conservation

Species	Match	AA	Alignment
Human		202	G	N	N	P	R	V	G	T	K	R	Y	M	A	P	E	V	L	D	E	Q	I	R	T	D
mutated	all conserved	202	G	N	N	P	R	V	G	T	K	R	Y	V	A	P	E	V	L	D	E	Q	I	R	T
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)	7.899	1
	9.317	1
(flanking)	8.01	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

12

Strand

1

Original gDNA sequence snippet

GAGTGGGCACCAAGCGGTACATGGCACCCGAGGTGCTGGAC

Altered gDNA sequence snippet

GAGTGGGCACCAAGCGGTACGTGGCACCCGAGGTGCTGGAC

Original cDNA sequence snippet

GAGTGGGCACCAAGCGGTACATGGCACCCGAGGTGCTGGAC

Altered cDNA sequence snippet

GAGTGGGCACCAAGCGGTACGTGGCACCCGAGGTGCTGGAC

Wildtype AA sequence

MALTPPLLLL SAGTMTLGSP RKGLLMLLMA LVTQGKGRYG EVWRGLWHGE SVAVKIFSSR
DEQSWFRETE IYNTVLLRHD NILGFIASDM TSRNSSTQLW LITHYHEHGS LYDFLQRQTL
EPHLALRLAV SAACGLAHLH VEIFGTQGKP AIAHRDFKSR NVLVKSNLQC CIADLGLAVM
HSQGSDYLDI GNNPRVGTKR YMAPEVLDEQ IRTDCFESYK WTDIWAFGLV LWEIARRTIV
NGIVEDYRPP FYDVVPNDPS FEDMKKVVCV DQQTPTIPNR LAADPVLSGL AQMMRECWYP
NPSARLTALR IKKTLQKISN SPEKPKVIQ*

Mutated AA sequence

MALTPPLLLL SAGTMTLGSP RKGLLMLLMA LVTQGKGRYG EVWRGLWHGE SVAVKIFSSR
DEQSWFRETE IYNTVLLRHD NILGFIASDM TSRNSSTQLW LITHYHEHGS LYDFLQRQTL
EPHLALRLAV SAACGLAHLH VEIFGTQGKP AIAHRDFKSR NVLVKSNLQC CIADLGLAVM
HSQGSDYLDI GNNPRVGTKR YVAPEVLDEQ IRTDCFESYK WTDIWAFGLV LWEIARRTIV
NGIVEDYRPP FYDVVPNDPS FEDMKKVVCV DQQTPTIPNR LAADPVLSGL AQMMRECWYP
NPSARLTALR IKKTLQKISN SPEKPKVIQ*

Position of stopcodon in wt / mu CDS

990 / 990

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

330 / 330

Position of stopcodon in wt / mu cDNA

1052 / 1052

Position of start ATG in wt / mu cDNA

63 / 63

Last intron/exon boundary

917

Theoretical NMD boundary in CDS

804

Length of CDS

990

Coding sequence (CDS) position

604

cDNA position

666

gDNA position

9206

Chromosomal position

51916113

Speed

0.04 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:

12:51916113A>G_1_ENST00000552678

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Known disease mutation: ClinVar ID 464754 (pathogenic)

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

Analysed issue

Analysis result

Variant

Chr12:51916113A>G (GRCh38)

Gene symbol

Gene constraints

LOEUF: 0.54, LOF (oe): 0.17, misssense (oe): 0.59, synonymous (oe): 0.88 ? (gnomAD)

Ensembl transcript ID

ENST00000552678.2

Genbank transcript ID

NM_001406488 (by similarity), NM_001406489 (by similarity), NM_001406493 (by similarity)

UniProt / AlphaMissense peptide

N/A

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.1126A>G
g.9206A>G

AA changes

AAE:	M376V	?
Score:	21

Frameshift

No

Length of protein

Normal

Pathogenic variant (ClinVar)

Cardiovascular phenotype
Telangiectasia, hereditary hemorrhagic, type 2

pathogenic

Variant DBs

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

Protein conservation

Species	Match	AA	Alignment
Human		376	G	N	N	P	R	V	G	T	K	R	Y	M	A	P	E	V	L	D	E	Q	I	R	T	D
mutated	all conserved	376	G	N	N	P	R	V	G	T	K	R	Y	V	A	P	E	V	L	D	E	Q	I	R	T
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)	7.899	1
	9.317	1
(flanking)	8.01	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

12

Strand

1

Original gDNA sequence snippet

GAGTGGGCACCAAGCGGTACATGGCACCCGAGGTGCTGGAC

Altered gDNA sequence snippet

GAGTGGGCACCAAGCGGTACGTGGCACCCGAGGTGCTGGAC

Original cDNA sequence snippet

GAGTGGGCACCAAGCGGTACATGGCACCCGAGGTGCTGGAC

Altered cDNA sequence snippet

GAGTGGGCACCAAGCGGTACGTGGCACCCGAGGTGCTGGAC

Wildtype AA sequence

MTLGSPRKGL LMLLMALVTQ GDPVKPSRGP LVTCTCESPH CKGPTCRGAW CTVVLVREEG
RHPQEHRGCG NLHRELCRGR PTEFVNHYCC DSHLCNHNVS LVLEATQPPS EQPGTDGQLA
LILGPVLALL ALVALGVLGL WHVRRRQEKQ RGLHSELGES SLILKASEQG DSMLGDLLDS
DCTTGSGSGL PFLVQRTVAR QVALVECVGK GRYGEVWRGL WHGESVAVKI FSSRDEQSWF
RETEIYNTVL LRHDNILGFI ASDMTSRNSS TQLWLITHYH EHGSLYDFLQ RQTLEPHLAL
RLAVSAACGL AHLHVEIFGT QGKPAIAHRD FKSRNVLVKS NLQCCIADLG LAVMHSQGSD
YLDIGNNPRV GTKRYMAPEV LDEQIRTDCF ESYKWTDIWA FGLVLWEIAR RTIVNGIVED
YRPPFYDVVP NDPSFEDMKK VVCVDQQTPT IPNRLAADPV RPLLGLGWRG VVAHGWDFWA
QELVSEASAS SHRY*

Mutated AA sequence

MTLGSPRKGL LMLLMALVTQ GDPVKPSRGP LVTCTCESPH CKGPTCRGAW CTVVLVREEG
RHPQEHRGCG NLHRELCRGR PTEFVNHYCC DSHLCNHNVS LVLEATQPPS EQPGTDGQLA
LILGPVLALL ALVALGVLGL WHVRRRQEKQ RGLHSELGES SLILKASEQG DSMLGDLLDS
DCTTGSGSGL PFLVQRTVAR QVALVECVGK GRYGEVWRGL WHGESVAVKI FSSRDEQSWF
RETEIYNTVL LRHDNILGFI ASDMTSRNSS TQLWLITHYH EHGSLYDFLQ RQTLEPHLAL
RLAVSAACGL AHLHVEIFGT QGKPAIAHRD FKSRNVLVKS NLQCCIADLG LAVMHSQGSD
YLDIGNNPRV GTKRYVAPEV LDEQIRTDCF ESYKWTDIWA FGLVLWEIAR RTIVNGIVED
YRPPFYDVVP NDPSFEDMKK VVCVDQQTPT IPNRLAADPV RPLLGLGWRG VVAHGWDFWA
QELVSEASAS SHRY*

Position of stopcodon in wt / mu CDS

1485 / 1485

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

495 / 495

Position of stopcodon in wt / mu cDNA

1565 / 1565

Position of start ATG in wt / mu cDNA

81 / 81

Last intron/exon boundary

1326

Theoretical NMD boundary in CDS

1195

Length of CDS

1485

Coding sequence (CDS) position

1126

cDNA position

1206

gDNA position

9206

Chromosomal position

51916113

Speed

0.06 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:

12:51916113A>G_4_ENST00000547400

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Known disease mutation: ClinVar ID 464754 (pathogenic)

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

Analysed issue

Analysis result

Variant

Chr12:51916113A>G (GRCh38)

Gene symbol

Gene constraints

LOEUF: 1.03, LOF (oe): 0.57, misssense (oe): 0.80, synonymous (oe): 1.06 ? (gnomAD)

Ensembl transcript ID

ENST00000547400.6

Genbank transcript ID

NM_001406491 (by similarity), NM_001406490 (by similarity), NM_001406492 (by similarity), NM_001406494 (by similarity)

UniProt / AlphaMissense peptide

N/A

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.856A>G
g.9206A>G

AA changes

AAE:	M286V	?
Score:	21

Frameshift

No

Length of protein

Normal

Pathogenic variant (ClinVar)

Cardiovascular phenotype
Telangiectasia, hereditary hemorrhagic, type 2

pathogenic

Variant DBs

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

Protein conservation

Species	Match	AA	Alignment
Human		286	G	N	N	P	R	V	G	T	K	R	Y	M	A	P	E	V	L	D	E	Q	I	R	T	D
mutated	all conserved	286	G	N	N	P	R	V	G	T	K	R	Y	V	A	P	E	V	L	D	E	Q	I	R	T
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)	7.899	1
	9.317	1
(flanking)	8.01	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

12

Strand

1

Original gDNA sequence snippet

GAGTGGGCACCAAGCGGTACATGGCACCCGAGGTGCTGGAC

Altered gDNA sequence snippet

GAGTGGGCACCAAGCGGTACGTGGCACCCGAGGTGCTGGAC

Original cDNA sequence snippet

GAGTGGGCACCAAGCGGTACATGGCACCCGAGGTGCTGGAC

Altered cDNA sequence snippet

GAGTGGGCACCAAGCGGTACGTGGCACCCGAGGTGCTGGAC

Wildtype AA sequence

MALTPPLLLL SAGTMTLGSP RKGLLMLLMA LVTQGDPVKP SRGPLVTCTC ESPHCKGPTC
RGAWCTVVLV REEGRHPQEH RGCGNLHREL CRGRPTEFVN HYCCDSHLCN HNVSLVLEGK
GRYGEVWRGL WHGESVAVKI FSSRDEQSWF RETEIYNTVL LRHDNILGFI ASDMTSRNSS
TQLWLITHYH EHGSLYDFLQ RQTLEPHLAL RLAVSAACGL AHLHVEIFGT QGKPAIAHRD
FKSRNVLVKS NLQCCIADLG LAVMHSQGSD YLDIGNNPRV GTKRYMAPEV LDEQIRTDCF
ESYKWTDIWA FGLVLWEIAR RTIVNGIVED YRPPFYDVVP NDPSFEDMKK VVCVDQQTPT
IPNRLAADPV LSGLAQMMRE CWYPNPSARL TALRIKKTLQ KISNSPEKPK VIQ*

Mutated AA sequence

MALTPPLLLL SAGTMTLGSP RKGLLMLLMA LVTQGDPVKP SRGPLVTCTC ESPHCKGPTC
RGAWCTVVLV REEGRHPQEH RGCGNLHREL CRGRPTEFVN HYCCDSHLCN HNVSLVLEGK
GRYGEVWRGL WHGESVAVKI FSSRDEQSWF RETEIYNTVL LRHDNILGFI ASDMTSRNSS
TQLWLITHYH EHGSLYDFLQ RQTLEPHLAL RLAVSAACGL AHLHVEIFGT QGKPAIAHRD
FKSRNVLVKS NLQCCIADLG LAVMHSQGSD YLDIGNNPRV GTKRYVAPEV LDEQIRTDCF
ESYKWTDIWA FGLVLWEIAR RTIVNGIVED YRPPFYDVVP NDPSFEDMKK VVCVDQQTPT
IPNRLAADPV LSGLAQMMRE CWYPNPSARL TALRIKKTLQ KISNSPEKPK VIQ*

Position of stopcodon in wt / mu CDS

1242 / 1242

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

414 / 414

Position of stopcodon in wt / mu cDNA

1346 / 1346

Position of start ATG in wt / mu cDNA

105 / 105

Last intron/exon boundary

1211

Theoretical NMD boundary in CDS

1056

Length of CDS

1242

Coding sequence (CDS) position

856

cDNA position

960

gDNA position

9206

Chromosomal position

51916113

Speed

0.05 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:

12:51916113A>G_6_ENST00000713619

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Known disease mutation: ClinVar ID 464754 (pathogenic)

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

Analysed issue

Analysis result

Variant

Chr12:51916113A>G (GRCh38)

Gene symbol

Gene constraints

no data

Ensembl transcript ID

ENST00000713619.1

Genbank transcript ID

UniProt / AlphaMissense peptide

N/A

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.1021A>G
g.9206A>G

AA changes

AAE:	M341V	?
Score:	21

Frameshift

No

Length of protein

Normal

Pathogenic variant (ClinVar)

Cardiovascular phenotype
Telangiectasia, hereditary hemorrhagic, type 2

pathogenic

Variant DBs

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

Protein conservation

Species	Match	AA	Alignment
Human		341	G	N	N	P	R	V	G	T	K	R	Y	M	A	P	E	V	L	D	E	Q	I	R	T	D
mutated	all conserved	341	G	N	N	P	R	V	G	T	K	R	Y	V	A	P	E	V	L	D	E	Q	I	R	T
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)	7.899	1
	9.317	1
(flanking)	8.01	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

12

Strand

1

Original gDNA sequence snippet

GAGTGGGCACCAAGCGGTACATGGCACCCGAGGTGCTGGAC

Altered gDNA sequence snippet

GAGTGGGCACCAAGCGGTACGTGGCACCCGAGGTGCTGGAC

Original cDNA sequence snippet

GAGTGGGCACCAAGCGGTACATGGCACCCGAGGTGCTGGAC

Altered cDNA sequence snippet

GAGTGGGCACCAAGCGGTACGTGGCACCCGAGGTGCTGGAC

Wildtype AA sequence

MTLGSPRKGL LMLLMALVTQ GDPVKPSRGP LVTCTCESPH CKGPTCRGAW CTVVLVREEG
RHPQEHRGCG NLHRELCRGR PTEFVNHYCC DSHLCNHNVS LVLEATQPPS EQPGTDGQLA
LILGPVLALL ALVALGVLGL WHVRRRQEKQ RGLHSELGES SLILKASEQG DSMLGDLLDS
DCTTGSGSGL PFLVQRTVAR QVALVECVGK GRYGEVWRGL WHGFIASDMT SRNSSTQLWL
ITHYHEHGSL YDFLQRQTLE PHLALRLAVS AACGLAHLHV EIFGTQGKPA IAHRDFKSRN
VLVKSNLQCC IADLGLAVMH SQGSDYLDIG NNPRVGTKRY MAPEVLDEQI RTDCFESYKW
TDIWAFGLVL WEIARRTIVN GIVEDYRPPF YDVVPNDPSF EDMKKVVCVD QQTPTIPNRL
AADPVLSGLA QMMRECWYPN PSARLTALRI KKTLQKISNS PEKPKVIQ*

Mutated AA sequence

MTLGSPRKGL LMLLMALVTQ GDPVKPSRGP LVTCTCESPH CKGPTCRGAW CTVVLVREEG
RHPQEHRGCG NLHRELCRGR PTEFVNHYCC DSHLCNHNVS LVLEATQPPS EQPGTDGQLA
LILGPVLALL ALVALGVLGL WHVRRRQEKQ RGLHSELGES SLILKASEQG DSMLGDLLDS
DCTTGSGSGL PFLVQRTVAR QVALVECVGK GRYGEVWRGL WHGFIASDMT SRNSSTQLWL
ITHYHEHGSL YDFLQRQTLE PHLALRLAVS AACGLAHLHV EIFGTQGKPA IAHRDFKSRN
VLVKSNLQCC IADLGLAVMH SQGSDYLDIG NNPRVGTKRY VAPEVLDEQI RTDCFESYKW
TDIWAFGLVL WEIARRTIVN GIVEDYRPPF YDVVPNDPSF EDMKKVVCVD QQTPTIPNRL
AADPVLSGLA QMMRECWYPN PSARLTALRI KKTLQKISNS PEKPKVIQ*

Position of stopcodon in wt / mu CDS

1407 / 1407

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

469 / 469

Position of stopcodon in wt / mu cDNA

1611 / 1611

Position of start ATG in wt / mu cDNA

205 / 205

Last intron/exon boundary

1476

Theoretical NMD boundary in CDS

1221

Length of CDS

1407

Coding sequence (CDS) position

1021

cDNA position

1225

gDNA position

9206

Chromosomal position

51916113

Speed

0.03 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