ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2735G>T (p.Gly912Val)

dbSNP: rs867959512
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001243126 SCV001416262 uncertain significance Hypertrophic cardiomyopathy 2019-10-18 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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"). This variant has been observed in an individual affected with hypertrophic cardiomyopathy (PMID: 24793961). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces glycine with valine at codon 912 of the MYBPC3 protein (p.Gly912Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine.
Ambry Genetics RCV002436956 SCV002748096 uncertain significance Cardiovascular phenotype 2021-11-08 criteria provided, single submitter clinical testing The p.G912V variant (also known as c.2735G>T), located in coding exon 26 of the MYBPC3 gene, results from a G to T substitution at nucleotide position 2735. The glycine at codon 912 is replaced by valine, an amino acid with dissimilar properties. This variant has been detected in a hypertrophic cardiomyopathy cohort; however, details were limited (Bos JM et al. Mayo Clin Proc, 2014 Jun;89:727-37). This amino acid position is highly 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.
GeneDx RCV004719112 SCV005325823 uncertain significance not provided 2024-03-13 criteria provided, single submitter clinical testing Identified in a patient with HCM in published literature (PMID: 24793961); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis supports a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 24793961)

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