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NM_001018005.2(TPM1):c.283G>A (p.Val95Ile) AND Hypertrophic cardiomyopathy

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Feb 20, 2022
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:
RCV002976684.3

Allele description [Variation Report for NM_001018005.2(TPM1):c.283G>A (p.Val95Ile)]

NM_001018005.2(TPM1):c.283G>A (p.Val95Ile)

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.283G>A (p.Val95Ile)
HGVS:
  • NC_000015.10:g.63057027G>A
  • NG_007557.1:g.19389G>A
  • NM_000366.6:c.283G>A
  • NM_001018004.2:c.283G>A
  • NM_001018005.2:c.283G>AMANE SELECT
  • NM_001018006.2:c.283G>A
  • NM_001018007.2:c.283G>A
  • NM_001018008.2:c.175G>A
  • NM_001018020.2:c.283G>A
  • NM_001301244.2:c.283G>A
  • NM_001301289.2:c.175G>A
  • NM_001330344.2:c.175G>A
  • NM_001330346.2:c.175G>A
  • NM_001330351.2:c.175G>A
  • NM_001365776.1:c.283G>A
  • NM_001365777.1:c.283G>A
  • NM_001365778.1:c.409G>A
  • NM_001365779.1:c.283G>A
  • NM_001365780.1:c.175G>A
  • NM_001365781.2:c.175G>A
  • NM_001365782.1:c.175G>A
  • NM_001407322.1:c.409G>A
  • NM_001407323.1:c.409G>A
  • NM_001407324.1:c.409G>A
  • NM_001407325.1:c.283G>A
  • NM_001407326.1:c.283G>A
  • NM_001407327.1:c.283G>A
  • NM_001407328.1:c.283G>A
  • NM_001407329.1:c.283G>A
  • NM_001407330.1:c.283G>A
  • NM_001407331.1:c.283G>A
  • NM_001407332.1:c.283G>A
  • NM_001407333.1:c.283G>A
  • NM_001407334.1:c.283G>A
  • NM_001407335.1:c.283G>A
  • NM_001407336.1:c.283G>A
  • NM_001407337.1:c.283G>A
  • NM_001407338.1:c.283G>A
  • NM_001407340.1:c.175G>A
  • NM_001407341.1:c.175G>A
  • NM_001407342.1:c.175G>A
  • NM_001407344.1:c.175G>A
  • NP_000357.3:p.Val95Ile
  • NP_001018004.1:p.Val95Ile
  • NP_001018005.1:p.Val95Ile
  • NP_001018006.1:p.Val95Ile
  • NP_001018007.1:p.Val95Ile
  • NP_001018008.1:p.Val59Ile
  • NP_001018020.1:p.Val95Ile
  • NP_001288173.1:p.Val95Ile
  • NP_001288218.1:p.Val59Ile
  • NP_001317273.1:p.Val59Ile
  • NP_001317275.1:p.Val59Ile
  • NP_001317280.1:p.Val59Ile
  • NP_001352705.1:p.Val95Ile
  • NP_001352706.1:p.Val95Ile
  • NP_001352707.1:p.Val137Ile
  • NP_001352708.1:p.Val95Ile
  • NP_001352709.1:p.Val59Ile
  • NP_001352710.1:p.Val59Ile
  • NP_001352711.1:p.Val59Ile
  • NP_001394251.1:p.Val137Ile
  • NP_001394252.1:p.Val137Ile
  • NP_001394253.1:p.Val137Ile
  • NP_001394254.1:p.Val95Ile
  • NP_001394255.1:p.Val95Ile
  • NP_001394256.1:p.Val95Ile
  • NP_001394257.1:p.Val95Ile
  • NP_001394258.1:p.Val95Ile
  • NP_001394259.1:p.Val95Ile
  • NP_001394260.1:p.Val95Ile
  • NP_001394261.1:p.Val95Ile
  • NP_001394262.1:p.Val95Ile
  • NP_001394263.1:p.Val95Ile
  • NP_001394264.1:p.Val95Ile
  • NP_001394265.1:p.Val95Ile
  • NP_001394266.1:p.Val95Ile
  • NP_001394267.1:p.Val95Ile
  • NP_001394269.1:p.Val59Ile
  • NP_001394270.1:p.Val59Ile
  • NP_001394271.1:p.Val59Ile
  • NP_001394273.1:p.Val59Ile
  • LRG_387t1:c.283G>A
  • LRG_387:g.19389G>A
  • LRG_387p1:p.Val95Ile
  • NC_000015.9:g.63349226G>A
  • NR_176337.1:n.366G>A
  • NR_176338.1:n.366G>A
  • NR_176339.1:n.461G>A
  • NR_176340.1:n.461G>A
  • NR_176341.1:n.366G>A
  • NR_176342.1:n.366G>A
  • NR_176343.1:n.366G>A
  • NR_176344.1:n.492G>A
  • NR_176345.1:n.366G>A
  • NR_176346.1:n.366G>A
  • NR_176347.1:n.366G>A
  • NR_176348.1:n.202G>A
  • NR_176349.1:n.202G>A
  • NR_176350.1:n.262G>A
  • NR_176351.1:n.262G>A
  • NR_176352.1:n.262G>A
  • NR_176353.1:n.262G>A
Protein change:
V137I
Molecular consequence:
  • NM_000366.6:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018004.2:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018005.2:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018006.2:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018007.2:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018008.2:c.175G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018020.2:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001301244.2:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001301289.2:c.175G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330344.2:c.175G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330346.2:c.175G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330351.2:c.175G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365776.1:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365777.1:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365778.1:c.409G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365779.1:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365780.1:c.175G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365781.2:c.175G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365782.1:c.175G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407322.1:c.409G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407323.1:c.409G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407324.1:c.409G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407325.1:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407326.1:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407327.1:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407328.1:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407329.1:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407330.1:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407331.1:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407332.1:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407333.1:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407334.1:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407335.1:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407336.1:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407337.1:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407338.1:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407340.1:c.175G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407341.1:c.175G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407342.1:c.175G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407344.1:c.175G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hypertrophic cardiomyopathy
Synonyms:
HYPERTROPHIC MYOCARDIOPATHY
Identifiers:
MONDO: MONDO:0005045; MeSH: D002312; MedGen: C0007194; Human Phenotype Ontology: HP:0001639

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003292649Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Feb 20, 2022) 		germlineclinical testing

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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003292649.2

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

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 95 of the TPM1 protein (p.Val95Ile). This missense change has been observed in individual(s) with dilated cardiomyopathy (Invitae). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Val95 amino acid residue in TPM1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11136687, 21295541, 21320446, 22187526). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0").

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

Last Updated: Sep 29, 2024