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NM_001018005.2(TPM1):c.188C>T (p.Ala63Val) AND not provided

Germline classification:
Likely pathogenic (2 submissions)
Last evaluated:
Jan 12, 2018
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:
RCV000024573.2

Allele description [Variation Report for NM_001018005.2(TPM1):c.188C>T (p.Ala63Val)]

NM_001018005.2(TPM1):c.188C>T (p.Ala63Val)

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.188C>T (p.Ala63Val)
HGVS:
  • NC_000015.10:g.63044100C>T
  • NG_007557.1:g.6462C>T
  • NM_000366.6:c.188C>T
  • NM_001018004.2:c.188C>T
  • NM_001018005.2:c.188C>TMANE SELECT
  • NM_001018006.2:c.188C>T
  • NM_001018007.2:c.240+269C>T
  • NM_001018020.2:c.240+269C>T
  • NM_001301244.2:c.240+269C>T
  • NM_001365776.1:c.188C>T
  • NM_001365777.1:c.188C>T
  • NM_001365778.1:c.314C>T
  • NM_001365779.1:c.188C>T
  • NP_000357.3:p.Ala63Val
  • NP_001018004.1:p.Ala63Val
  • NP_001018005.1:p.Ala63Val
  • NP_001018006.1:p.Ala63Val
  • NP_001352705.1:p.Ala63Val
  • NP_001352706.1:p.Ala63Val
  • NP_001352707.1:p.Ala105Val
  • NP_001352708.1:p.Ala63Val
  • LRG_387t1:c.188C>T
  • LRG_387:g.6462C>T
  • LRG_387p1:p.Ala63Val
  • NC_000015.9:g.63336299C>T
  • NM_001018005.1:c.188C>T
  • P09493:p.Ala63Val
  • p.(Ala63Val)
Protein change:
A105V
Links:
Leiden Muscular Dystrophy (TPM1): TPM1_00005; UniProtKB: P09493#VAR_013135; dbSNP: rs199476306
NCBI 1000 Genomes Browser:
rs199476306
Molecular consequence:
  • NM_001018007.2:c.240+269C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001018020.2:c.240+269C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001301244.2:c.240+269C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000366.6:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018004.2:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018005.2:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018006.2:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365776.1:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365777.1:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365778.1:c.314C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365779.1:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
functional variant [Sequence Ontology: SO:0001536]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000045879Leiden Muscular Dystrophy (TPM1)
no classification provided
not providedgermlinecuration

PubMed (2)
[See all records that cite these PMIDs]

SCV000589543GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Likely pathogenic
(Jan 12, 2018) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedcuration
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Novel missense mutation in alpha-tropomyosin gene found in Japanese patients with hypertrophic cardiomyopathy.

Nakajima-Taniguchi C, Matsui H, Nagata S, Kishimoto T, Yamauchi-Takihara K.

J Mol Cell Cardiol. 1995 Sep;27(9):2053-8.

PubMed [citation]
PMID:
8523464

Clinical implications of hypertrophic cardiomyopathy associated with mutations in the alpha-tropomyosin gene.

Yamauchi-Takihara K, Nakajima-Taniguchi C, Matsui H, Fujio Y, Kunisada K, Nagata S, Kishimoto T.

Heart. 1996 Jul;76(1):63-5.

PubMed [citation]
PMID:
8774330
PMCID:
PMC484428

Details of each submission

From Leiden Muscular Dystrophy (TPM1), SCV000045879.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From GeneDx, SCV000589543.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The A63V likely pathogenic variant in the TPM1 gene has been reported in multiple individuals with HCM (Nakajima-Taniguchi et al., 1995; Yamauchi-Takihara et al., 1996; Lopes et al., 2015). Additionally, A63V is classified as a likely pathogenic variant by another clinical laboratory in ClinVar (SCV000285666.2; Landrum et al., 2016). The A63V variant is not observed in large population cohorts (Lek et al., 2016). Although the A63V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties, functional studies show that the A63V variant destabilizes the tropomyosin protein and results in muscle cell dysfunction (Michele et al., 2002; Heller et al., 2003; Hilario et al., 2004).

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

Last Updated: May 1, 2024