Submissions for variant NM_000256.3(MYBPC3):c.3809T>G (p.Val1270Gly)

dbSNP: rs1064793310

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000479000	SCV000565730	uncertain significance	not provided	2017-02-21	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the MYBPC3 gene. The V1270G variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). 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, the V1270G variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties.
Invitae	RCV001351079	SCV001545512	uncertain significance	Hypertrophic cardiomyopathy	2024-01-17	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 1270 of the MYBPC3 protein (p.Val1270Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 418579). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.