ClinVar Miner

Submissions for variant NM_000363.5(TNNI3):c.562G>A (p.Val188Met)

dbSNP: rs193922409
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159240 SCV000209186 likely pathogenic not provided 2021-01-27 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar (ClinVar Variant ID# 36883; Landrum et al., 2016); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000625703 SCV000696596 uncertain significance not specified 2016-10-27 criteria provided, single submitter clinical testing Variant summary: The TNNI3 c.562G>A (p.Val188Met) variant involves the alteration of a conserved nucleotide. 4/5 in silico tools predict a damaging outcome for this substitution. This variant is absent in 120606 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Mutations in nearby residues (Asn185Lys, Arg186Gln, Glu187Gly, Asp190Gly, Arg192Cys) are listed in HGMD as causative variants for cardiomyopathy or atrial fibrillation indicating the functional importance of this region of the protein. A clinical diagnostic laboratory classified this variant as likely pathogenic (without evidence to independently evaluate). Due to the absence of clinical information about variant carriers and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV002513269 SCV003033799 uncertain significance Hypertrophic cardiomyopathy 2022-12-16 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 36883). This variant has not been reported in the literature in individuals affected with TNNI3-related conditions. 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 188 of the TNNI3 protein (p.Val188Met).
Mayo Clinic Laboratories, Mayo Clinic RCV000159240 SCV004225441 uncertain significance not provided 2022-02-11 criteria provided, single submitter clinical testing PP3, PM1, PM2_supporting

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