ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.758G>T (p.Gly253Val)

dbSNP: rs730880853
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158763 SCV000208698 uncertain significance not provided 2019-06-11 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV000620876 SCV000735493 uncertain significance Cardiovascular phenotype 2020-11-13 criteria provided, single submitter clinical testing The p.G253V variant (also known as c.758G>T), located in coding exon 7 of the MYH7 gene, results from a G to T substitution at nucleotide position 758. The glycine at codon 253 is replaced by valine, an amino acid with dissimilar properties, and is located in the head domain. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001850223 SCV002160691 uncertain significance Hypertrophic cardiomyopathy 2022-05-14 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 253 of the MYH7 protein (p.Gly253Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. ClinVar contains an entry for this variant (Variation ID: 181324). 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 C0"). This variant is found within a region of MYH7 between codons 181 and 937 that contains the majority of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). 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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