ClinVar Miner

Submissions for variant NM_000364.4(TNNT2):c.806A>G (p.Asn269Ser) (rs397516483)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000036619 SCV000060274 uncertain significance not specified 2018-04-23 criteria provided, single submitter clinical testing The p.Asn262Ser variant in TNNT2 has been reported in at least 6 individuals wit h HCM, and segregated with disease in 1 affected relative from 1 family (Ho 2009 , Walsh 2016, LMM data). However, one of these individuals and their affected fa mily member also carried an additional likely pathogenic variant in another HCM gene that could explain their disease (LMM data). This variant has also been rep orted by other clinical laboratories in ClinVar (Variation ID 43671) and has bee n identified in 1/90942 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/; dbSNP rs397516483). Asparagine (Asn) is not conserved in fish and the change to serine (Ser) was predicted to be ben ign using a computational tool clinically validated by our laboratory. This tool 's benign prediction is estimated to be correct 89% of the time (Jordan 2011). I n summary, the clinical significance of the p.Asn262Ser variant is uncertain. AC MG/AMP Criteria applied: PM2, PM4_Moderate, BP4.
Color RCV000777960 SCV000914061 uncertain significance Cardiomyopathy 2018-04-18 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This variant is a missense variant located in the tropomyosin binding domain of the TNNT2 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact the RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in several individuals affected with hypertrophic cardiomyopathy (PMID: 25524337, 26455666, 27552257). One of the patients also carried a duplication of the entire TNNT2 gene. This variant is rare in the general population and has been identified has been identified in 0/277264 chromosomes by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.

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