MutationT@ster 2025

NEVER press reload or F5 - unless you want to start from the very beginning.
Input seems to be ok - now mapping the variant to the different transcripts...
Querying Taster for transcript #1: ENST00000610404
Querying Taster for transcript #2: ENST00000649620
Querying Taster for transcript #3: ENST00000237014
MT speed 0.23 s - this script 2.642037 s

Transcript summary:

Permalink

Transcript	Gene symbol	Prediction	Tree vote	Model	Splice site change	Known ClinVar disease mutation	Variant type	Protein length	Features at a glance
ENST00000237014(MANE Select)	TTR	Deleterious	85\|15	simple_aae	No	Yes	Single base exchange	Normal	Amino acid sequence changed Known disease mutation: ClinVar ID 13417 (pathogenic) Protein features (might be) affected
ENST00000610404	TTR	Deleterious	89\|11	simple_aae	No	Yes	Single base exchange	Normal	Amino acid sequence changed Known disease mutation: ClinVar ID 13417 (pathogenic)
ENST00000649620	TTR	Deleterious	89\|11	simple_aae	No	Yes	Single base exchange	Normal	Amino acid sequence changed Known disease mutation: ClinVar ID 13417 (pathogenic) Protein features (might be) affected

MutationT@ster 2025

Variant:

18:31592974G>A_3_ENST00000237014

Back to summary table

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Known disease mutation: ClinVar ID 13417 (pathogenic)
Protein features (might be) affected

Model: simple_aae
Tree vote: 85|15 (del | benign) ?
Automatic classification due to ClinVar

Analysed issue

Analysis result

Variant

Chr18:31592974G>A (GRCh38)

Gene symbol

TTR

Gene constraints

LOEUF: 1.05, LOF (oe): 0.60, misssense (oe): 0.69, synonymous (oe): 0.99 ? (gnomAD)

Ensembl transcript ID

ENST00000237014.8

Genbank transcript ID

NM_000371 (exact from MANE)

UniProt / AlphaMissense peptide

TTHY_HUMAN | AlphaMissense: transcript, gene

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.148G>A
g.35966G>A

AA changes

AAE:	V50M	?
Score:	21

Frameshift

No

Length of protein

Normal

Pathogenic variant (ClinVar)

Cardiomyopathy
TTR-related disorder
Amyloidosis, hereditary systemic 1
Carpal tunnel syndrome 1
Hyperthyroxinemia, dystransthyretinemic
Cardiovascular phenotype
Charcot-Marie-Tooth disease

pathogenic

ClinVar OMIM

Variant DBs

dbSNP ID	rs28933979
gnomAD	homozygous (A/A)	heterozygous	allele carriers
	0	92	92

Protein conservation

Species	Match	AA	Alignment
Human		50	A	V	R	G	S	P	A	I	N	V	A	V	H	V	F	R	K	A	A	D	D	T	W	E
mutated	all conserved	50	A	V	R	G	S	P	A	I	N	V	A	M	H	V	F	R	K	A	A	D	D	T
Ptroglodytes	all identical	50	A	V	R	G	S	P	A	I	N	V	A	V	H	V	F	K	K	A	A	D	E	T
Mmulatta	all identical	52	A	V	R	G	S	P	A	V	N	V	A	V	N	V	F	K	K	A	A	D	E	T	W
Fcatus	all identical	50	A	V	Q	G	S	P	A	V	N	V	A	V	K	V	F	K	K	A	A	D	E	S
Mmusculus	all identical	50	A	V	R	G	S	P	A	V	D	V	A	V	K	V	F	K	K	T	S	E	G	S
Ggallus	all identical	216	A	V	R	G	S	P	A	A	N	V	A	V	K	V	F	K	K	A	A	D	G	T	W
Trubripes	all conserved	46	A	V	K	G	T	P	A	G	P	M	V	L	N	L	Y	Q	R	T	A	D	G	G	W
Drerio	no homologue
Dmelanogaster	no homologue
Celegans	no homologue
Xtropicalis	all identical	49	A	V	R	G	I	P	A	A	N	L	L	V	Q	V	F	R	N	T	-	E	G	N	W

Protein features

Start (aa)	End (aa)	Feature	Details
21	147	CHAIN		lost
49	55	STRAND		lost

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	-2.758	0
	2.829	0.997
(flanking)	4.476	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

18

Strand

1

Original gDNA sequence snippet

GTCCTGCCATCAATGTGGCCGTGCATGTGTTCAGAAAGGCT

Altered gDNA sequence snippet

GTCCTGCCATCAATGTGGCCATGCATGTGTTCAGAAAGGCT

Original cDNA sequence snippet

GTCCTGCCATCAATGTGGCCGTGCATGTGTTCAGAAAGGCT

Altered cDNA sequence snippet

GTCCTGCCATCAATGTGGCCATGCATGTGTTCAGAAAGGCT

Wildtype AA sequence

MASHRLLLLC LAGLVFVSEA GPTGTGESKC PLMVKVLDAV RGSPAINVAV HVFRKAADDT
WEPFASGKTS ESGELHGLTT EEEFVEGIYK VEIDTKSYWK ALGISPFHEH AEVVFTANDS
GPRRYTIAAL LSPYSYSTTA VVTNPKE*

Mutated AA sequence

MASHRLLLLC LAGLVFVSEA GPTGTGESKC PLMVKVLDAV RGSPAINVAM HVFRKAADDT
WEPFASGKTS ESGELHGLTT EEEFVEGIYK VEIDTKSYWK ALGISPFHEH AEVVFTANDS
GPRRYTIAAL LSPYSYSTTA VVTNPKE*

Position of stopcodon in wt / mu CDS

444 / 444

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

148 / 148

Position of stopcodon in wt / mu cDNA

470 / 470

Position of start ATG in wt / mu cDNA

27 / 27

Last intron/exon boundary

362

Theoretical NMD boundary in CDS

285

Length of CDS

444

Coding sequence (CDS) position

148

cDNA position

174

gDNA position

35966

Chromosomal position

31592974

Speed

0.09 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

Back to summary table

MutationT@ster 2025

Variant:

18:31592974G>A_1_ENST00000610404

Back to summary table

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Known disease mutation: ClinVar ID 13417 (pathogenic)

Model: simple_aae
Tree vote: 89|11 (del | benign) ?
Automatic classification due to ClinVar

Analysed issue

Analysis result

Variant

Chr18:31592974G>A (GRCh38)

Gene symbol

TTR

Gene constraints

LOEUF: 1.02, LOF (oe): 0.52, misssense (oe): 0.67, synonymous (oe): 0.95 ? (gnomAD)

Ensembl transcript ID

ENST00000610404.5

Genbank transcript ID

UniProt / AlphaMissense peptide

N/A

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.52G>A
g.35966G>A

AA changes

AAE:	V18M	?
Score:	21

Frameshift

No

Length of protein

Normal

Pathogenic variant (ClinVar)

Cardiomyopathy
TTR-related disorder
Amyloidosis, hereditary systemic 1
Carpal tunnel syndrome 1
Hyperthyroxinemia, dystransthyretinemic
Cardiovascular phenotype
Charcot-Marie-Tooth disease

pathogenic

ClinVar OMIM

Variant DBs

dbSNP ID	rs28933979
gnomAD	homozygous (A/A)	heterozygous	allele carriers
	0	92	92

Protein conservation

Species	Match	AA	Alignment
Human		18	A	V	R	G	S	P	A	I	N	V	A	V	H	V	F	R	K	A	A	D	D	T	W	E
mutated	all conserved	18	A	V	R	G	S	P	A	I	N	V	A	M	H	V	F	R	K	A	A	D	D	T	W
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)	-2.758	0
	2.829	0.997
(flanking)	4.476	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

18

Strand

1

Original gDNA sequence snippet

GTCCTGCCATCAATGTGGCCGTGCATGTGTTCAGAAAGGCT

Altered gDNA sequence snippet

GTCCTGCCATCAATGTGGCCATGCATGTGTTCAGAAAGGCT

Original cDNA sequence snippet

GTCCTGCCATCAATGTGGCCGTGCATGTGTTCAGAAAGGCT

Altered cDNA sequence snippet

GTCCTGCCATCAATGTGGCCATGCATGTGTTCAGAAAGGCT

Wildtype AA sequence

MVKVLDAVRG SPAINVAVHV FRKAADDTWE PFASGKTSES GELHGLTTEE EFVEGIYKVE
IDTKSYWKAL GISPFHEHAE VVFTANDSGP RRYTIAALLS PYSYSTTAVV TNPKE*

Mutated AA sequence

MVKVLDAVRG SPAINVAMHV FRKAADDTWE PFASGKTSES GELHGLTTEE EFVEGIYKVE
IDTKSYWKAL GISPFHEHAE VVFTANDSGP RRYTIAALLS PYSYSTTAVV TNPKE*

Position of stopcodon in wt / mu CDS

348 / 348

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

116 / 116

Position of stopcodon in wt / mu cDNA

498 / 498

Position of start ATG in wt / mu cDNA

151 / 151

Last intron/exon boundary

390

Theoretical NMD boundary in CDS

189

Length of CDS

348

Coding sequence (CDS) position

52

cDNA position

202

gDNA position

35966

Chromosomal position

31592974

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

Back to summary table

MutationT@ster 2025

Variant:

18:31592974G>A_2_ENST00000649620

Back to summary table

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Known disease mutation: ClinVar ID 13417 (pathogenic)
Protein features (might be) affected

Model: simple_aae
Tree vote: 89|11 (del | benign) ?
Automatic classification due to ClinVar

Analysed issue

Analysis result

Variant

Chr18:31592974G>A (GRCh38)

Gene symbol

TTR

Gene constraints

LOEUF: 1.05, LOF (oe): 0.60, misssense (oe): 0.69, synonymous (oe): 0.99 ? (gnomAD)

Ensembl transcript ID

ENST00000649620.1

Genbank transcript ID

UniProt / AlphaMissense peptide

TTHY_HUMAN | AlphaMissense: transcript, gene

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.148G>A
g.35966G>A

AA changes

AAE:	V50M	?
Score:	21

Frameshift

No

Length of protein

Normal

Pathogenic variant (ClinVar)

Cardiomyopathy
TTR-related disorder
Amyloidosis, hereditary systemic 1
Carpal tunnel syndrome 1
Hyperthyroxinemia, dystransthyretinemic
Cardiovascular phenotype
Charcot-Marie-Tooth disease

pathogenic

ClinVar OMIM

Variant DBs

dbSNP ID	rs28933979
gnomAD	homozygous (A/A)	heterozygous	allele carriers
	0	92	92

Protein conservation

Species	Match	AA	Alignment
Human		50	A	V	R	G	S	P	A	I	N	V	A	V	H	V	F	R	K	A	A	D	D	T	W	E
mutated	all conserved	50	A	V	R	G	S	P	A	I	N	V	A	M	H	V	F	R	K	A	A	D	D	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
21	147	CHAIN		lost
49	55	STRAND		lost

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	-2.758	0
	2.829	0.997
(flanking)	4.476	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

18

Strand

1

Original gDNA sequence snippet

GTCCTGCCATCAATGTGGCCGTGCATGTGTTCAGAAAGGCT

Altered gDNA sequence snippet

GTCCTGCCATCAATGTGGCCATGCATGTGTTCAGAAAGGCT

Original cDNA sequence snippet

GTCCTGCCATCAATGTGGCCGTGCATGTGTTCAGAAAGGCT

Altered cDNA sequence snippet

GTCCTGCCATCAATGTGGCCATGCATGTGTTCAGAAAGGCT

Wildtype AA sequence

MASHRLLLLC LAGLVFVSEA GPTGTGESKC PLMVKVLDAV RGSPAINVAV HVFRKAADDT
WEPFASGKTS ESGELHGLTT EEEFVEGIYK VEIDTKSYWK ALGISPFHEH AEVVFTANDS
GPRRYTIAAL LSPYSYSTTA VVTNPKE*

Mutated AA sequence

MASHRLLLLC LAGLVFVSEA GPTGTGESKC PLMVKVLDAV RGSPAINVAM HVFRKAADDT
WEPFASGKTS ESGELHGLTT EEEFVEGIYK VEIDTKSYWK ALGISPFHEH AEVVFTANDS
GPRRYTIAAL LSPYSYSTTA VVTNPKE*

Position of stopcodon in wt / mu CDS

444 / 444

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

148 / 148

Position of stopcodon in wt / mu cDNA

667 / 667

Position of start ATG in wt / mu cDNA

224 / 224

Last intron/exon boundary

559

Theoretical NMD boundary in CDS

285

Length of CDS

444

Coding sequence (CDS) position

148

cDNA position

371

gDNA position

35966

Chromosomal position

31592974

Speed

0.10 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

Back to summary table