ClinVar Miner

Submissions for variant NM_001276345.2(TNNT2):c.208A>G (p.Met70Val) (rs141837529)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000036559 SCV000060214 likely benign not specified 2014-11-13 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
GeneDx RCV000766663 SCV000520039 uncertain significance not provided 2018-07-11 criteria provided, single submitter clinical testing The M60V variant of uncertain significance in the TNNT2 gene has been previously reported in association with HCM (Walsh et al., 2017), although no detailed clinical information or segregation data were provided. This variant is observed in 8/24,020 (0.03%) alleles from individuals of African ancestry in large population cohorts (Lek et al., 2016). The M60V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Moreover, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000766663 SCV001150583 likely benign not provided 2018-05-01 criteria provided, single submitter clinical testing
Invitae RCV001056318 SCV001220756 uncertain significance Familial hypertrophic cardiomyopathy 2; Left ventricular noncompaction 6; Familial restrictive cardiomyopathy 3 2020-09-08 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 60 of the TNNT2 protein (p.Met60Val). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and valine. This variant is present in population databases (rs141837529, ExAC 0.04%). This variant has been observed in an individual affected with dilated cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 43615). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Color Health, Inc RCV001189707 SCV001357057 likely benign Cardiomyopathy 2019-03-27 criteria provided, single submitter clinical testing

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