ClinVar Miner

Submissions for variant NM_000363.5(TNNI3):c.488C>T (p.Ala163Val) (rs727504367)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001348309 SCV001542607 uncertain significance Hypertrophic cardiomyopathy 2020-04-20 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 163 of the TNNI3 protein (p.Ala163Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of dilated cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 177866). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.
GeneDx RCV001541094 SCV001759050 likely pathogenic not provided 2020-01-07 criteria provided, single submitter clinical testing Identified in association with DCM in published literature (Walsh et al., 2017), and a patient referred for cardiomyopathy genetic testing at GeneDx; Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 177866; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 27532257)
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000154504 SCV000204175 uncertain significance not specified 2013-01-23 no assertion criteria provided clinical testing proposed classification - variant undergoing re-assessment, contact laboratory

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