ClinVar Miner

Submissions for variant NM_000364.4(TNNT2):c.110C>G (p.Ala37Gly)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000700417 SCV000829171 uncertain significance Familial hypertrophic cardiomyopathy 2; Left ventricular noncompaction 6; Familial restrictive cardiomyopathy 3 2018-04-18 criteria provided, single submitter clinical testing This sequence change replaces alanine with glycine at codon 27 of the TNNT2 protein (p.Ala27Gly). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and glycine. This variant is present in population databases (rs776406819, ExAC 0.02%). This variant has not been reported in the literature in individuals with TNNT2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; Align-GVGD: "Class C0". The glycine 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.
Integrated Genetics/Laboratory Corporation of America RCV000781910 SCV000920313 uncertain significance not specified 2018-11-15 criteria provided, single submitter clinical testing Variant summary: TNNT2 c.80C>G (p.Ala27Gly) results in a non-conservative amino acid change in the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 246226 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.80C>G in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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