U.S. flag

An official website of the United States government

NM_001018005.2(TPM1):c.284T>C (p.Val95Ala) AND Cardiovascular phenotype

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Sep 25, 2020
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000619092.4

Allele description [Variation Report for NM_001018005.2(TPM1):c.284T>C (p.Val95Ala)]

NM_001018005.2(TPM1):c.284T>C (p.Val95Ala)

Gene:
TPM1:tropomyosin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q22.2
Genomic location:
Preferred name:
NM_001018005.2(TPM1):c.284T>C (p.Val95Ala)
Other names:
p.V95A:GTT>GCT
HGVS:
  • NC_000015.10:g.63057028T>C
  • NG_007557.1:g.19390T>C
  • NM_000366.6:c.284T>C
  • NM_001018004.2:c.284T>C
  • NM_001018005.2:c.284T>CMANE SELECT
  • NM_001018006.2:c.284T>C
  • NM_001018007.2:c.284T>C
  • NM_001018008.2:c.176T>C
  • NM_001018020.2:c.284T>C
  • NM_001301244.2:c.284T>C
  • NM_001301289.2:c.176T>C
  • NM_001330344.2:c.176T>C
  • NM_001330346.2:c.176T>C
  • NM_001330351.2:c.176T>C
  • NM_001365776.1:c.284T>C
  • NM_001365777.1:c.284T>C
  • NM_001365778.1:c.410T>C
  • NM_001365779.1:c.284T>C
  • NM_001365780.1:c.176T>C
  • NM_001365781.2:c.176T>C
  • NM_001365782.1:c.176T>C
  • NP_000357.3:p.Val95Ala
  • NP_001018004.1:p.Val95Ala
  • NP_001018005.1:p.Val95Ala
  • NP_001018006.1:p.Val95Ala
  • NP_001018007.1:p.Val95Ala
  • NP_001018008.1:p.Val59Ala
  • NP_001018020.1:p.Val95Ala
  • NP_001288173.1:p.Val95Ala
  • NP_001288218.1:p.Val59Ala
  • NP_001317273.1:p.Val59Ala
  • NP_001317275.1:p.Val59Ala
  • NP_001317280.1:p.Val59Ala
  • NP_001352705.1:p.Val95Ala
  • NP_001352706.1:p.Val95Ala
  • NP_001352707.1:p.Val137Ala
  • NP_001352708.1:p.Val95Ala
  • NP_001352709.1:p.Val59Ala
  • NP_001352710.1:p.Val59Ala
  • NP_001352711.1:p.Val59Ala
  • LRG_387t1:c.284T>C
  • LRG_387:g.19390T>C
  • LRG_387p1:p.Val95Ala
  • NC_000015.9:g.63349227T>C
  • NM_000366.5:c.284T>C
  • NM_001018005.1:c.284T>C
  • p.(Val95Ala)
Protein change:
V137A; VAL95ALA
Links:
Leiden Muscular Dystrophy (TPM1): TPM1_00007; OMIM: 191010.0003; dbSNP: rs104894504
NCBI 1000 Genomes Browser:
rs104894504
Molecular consequence:
  • NM_000366.6:c.284T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018004.2:c.284T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018005.2:c.284T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018006.2:c.284T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018007.2:c.284T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018008.2:c.176T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018020.2:c.284T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001301244.2:c.284T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001301289.2:c.176T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330344.2:c.176T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330346.2:c.176T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330351.2:c.176T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365776.1:c.284T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365777.1:c.284T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365778.1:c.410T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365779.1:c.284T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365780.1:c.176T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365781.2:c.176T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365782.1:c.176T>C - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
functional variant [Sequence Ontology: SO:0001536]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000740262Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Sep 25, 2020) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Hypertrophic cardiomyopathy caused by a novel alpha-tropomyosin mutation (V95A) is associated with mild cardiac phenotype, abnormal calcium binding to troponin, abnormal myosin cycling, and poor prognosis.

Karibe A, Tobacman LS, Strand J, Butters C, Back N, Bachinski LL, Arai AE, Ortiz A, Roberts R, Homsher E, Fananapazir L.

Circulation. 2001 Jan 2;103(1):65-71.

PubMed [citation]
PMID:
11136687

Several cardiomyopathy causing mutations on tropomyosin either destabilize the active state of actomyosin or alter the binding properties of tropomyosin.

Mathur MC, Chase PB, Chalovich JM.

Biochem Biophys Res Commun. 2011 Mar 4;406(1):74-8. doi: 10.1016/j.bbrc.2011.01.112. Epub 2011 Feb 3.

PubMed [citation]
PMID:
21295541
PMCID:
PMC3057449
See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000740262.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

The p.V95A variant (also known as c.284T>C), located in coding exon 3 of the TPM1 gene, results from a T to C substitution at nucleotide position 284. The valine at codon 95 is replaced by alanine, an amino acid with similar properties. This alteration was reported to segregate with hypertrophic cardiomyopathy in a multi-generation family with reduced penetrance (Karibe A et al. Circulation, 2001 Jan;103:65-71). This variant has also been detected in a dilated cardiomypathy cohort (Hazebroek MR et al. Circ Heart Fail. 2018 03;11(3):e004682). In vitro assays suggested that this mutant would affect protein structure and function (Karibe A et al. Circulation, 2001 Jan;103:65-71; Bai F et al. Biophys. J., 2011 Feb;100:1014-23; Mathur MC et al. Biochem. Biophys. Res. Commun., 2011 Mar;406:74-8; Wang F et al. J. Biomed. Biotechnol., 2011 Dec;2011:435271). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 16, 2024