ClinVar Miner

Submissions for variant NM_000364.4(TNNT2):c.502C>G (p.Arg168Gly) (rs730881103)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159300 SCV000209246 uncertain significance not provided 2016-07-19 criteria provided, single submitter clinical testing The R158G variant has been reported previously in one Chinese proband with HCM; additional clinical information and segregation data was not provided (Zou et al., 2013). The R158G variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R158G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Furthermore, this substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, additional evidence is needed to determine whether this variant is pathogenic or benign.
Invitae RCV000646065 SCV000767822 uncertain significance Familial hypertrophic cardiomyopathy 2; Left ventricular noncompaction 6; Familial restrictive cardiomyopathy 3 2017-08-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 158 of the TNNT2 protein (p.Arg158Gly). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 23283745). ClinVar contains an entry for this variant (Variation ID: 181620). A computational algorithm designed to assess the pathogenicity of variants in TNNT2 with regard to hypertrophic cardiomyopathy predicted this sequence change to be deleterious. The algorithm has a sensitivity of 94% and a specificity of 89% (PMID: 21310275). 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.

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