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NM_001276345.2(TNNT2):c.283G>A (p.Val95Met) AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Apr 7, 2023
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:
RCV001987101.4

Allele description [Variation Report for NM_001276345.2(TNNT2):c.283G>A (p.Val95Met)]

NM_001276345.2(TNNT2):c.283G>A (p.Val95Met)

Gene:
TNNT2:troponin T2, cardiac type [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q32.1
Genomic location:
Preferred name:
NM_001276345.2(TNNT2):c.283G>A (p.Val95Met)
HGVS:
  • NC_000001.11:g.201365621C>T
  • NG_007556.1:g.17057G>A
  • NM_000364.4:c.283G>A
  • NM_001001430.3:c.253G>A
  • NM_001001431.3:c.253G>A
  • NM_001001432.3:c.238G>A
  • NM_001276345.2:c.283G>AMANE SELECT
  • NM_001276346.2:c.280G>A
  • NM_001276347.2:c.253G>A
  • NP_000355.2:p.Val95Met
  • NP_001001430.1:p.Val85Met
  • NP_001001431.1:p.Val85Met
  • NP_001001432.1:p.Val80Met
  • NP_001263274.1:p.Val95Met
  • NP_001263275.1:p.Val94Met
  • NP_001263276.1:p.Val85Met
  • LRG_431t1:c.283G>A
  • LRG_431:g.17057G>A
  • LRG_431p1:p.Val95Met
  • NC_000001.10:g.201334749C>T
  • NM_001276345.2:c.283G>A
Protein change:
V80M
Links:
dbSNP: rs1659515084
NCBI 1000 Genomes Browser:
rs1659515084
Molecular consequence:
  • NM_000364.4:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001430.3:c.253G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001431.3:c.253G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001432.3:c.238G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276345.2:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276346.2:c.280G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276347.2:c.253G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hypertrophic cardiomyopathy 2
Synonyms:
Familial hypertrophic cardiomyopathy 2; TNNT2-Related Familial Hypertrophic Cardiomyopathy
Identifiers:
MONDO: MONDO:0007266; MedGen: C1861864; OMIM: 115195
Name:
Dilated cardiomyopathy 1D
Synonyms:
Left ventricular noncompaction 6
Identifiers:
MONDO: MONDO:0011095; MedGen: C1832243; Orphanet: 154; Orphanet: 54260; OMIM: 601494
Name:
Cardiomyopathy, familial restrictive, 3
Identifiers:
MONDO: MONDO:0012900; MedGen: C2676271; Orphanet: 75249; OMIM: 612422

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002212936Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Apr 7, 2023) 		germlineclinical testing

PubMed (2)
[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

A child cohort study from southern Italy enlarges the genetic spectrum of hypertrophic cardiomyopathy.

Frisso G, Limongelli G, Pacileo G, Del Giudice A, Forgione L, Calabrò P, Iacomino M, Detta N, Di Fonzo LM, Maddaloni V, Calabrò R, Salvatore F.

Clin Genet. 2009 Jul;76(1):91-101. doi: 10.1111/j.1399-0004.2009.01190.x.

PubMed [citation]
PMID:
19659763

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002212936.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TNNT2 protein function. ClinVar contains an entry for this variant (Variation ID: 1435754). This variant is also known as c.283G>A (p.V95M). This missense change has been observed in individuals with hypertrophic cardiomyopathy (PMID: 19659763; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 85 of the TNNT2 protein (p.Val85Met).

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

Last Updated: Oct 26, 2024