ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.787G>A (p.Gly263Arg) (rs373730381)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000412865 SCV000490635 uncertain significance not provided 2016-05-27 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MYBPC3 gene. The Gly263Arg variant has been reported as a de novo variant in one patient with HCM and was absent from 120 control individuals; however, functional studies and detailed clinical information were not provided. It was not observed with any significant frequency in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project10, indicating it is not a common benign variant in these populations. The Gly263Arg 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. However, this substitution occurs at a position that is not conserved across species and in silico analysis predicts this variant likely does not alter the protein structure/function.
Invitae RCV000528899 SCV000623621 uncertain significance Hypertrophic cardiomyopathy 2018-09-20 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 263 of the MYBPC3 protein (p.Gly263Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs373730381, ExAC 0.2%). This variant has been observed to be de novo in an individual affected with hypertrophic cardiomyopathy (PMID: 15563892). ClinVar contains an entry for this variant (Variation ID: 161315). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV000617282 SCV000740241 uncertain significance Cardiovascular phenotype 2017-10-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770378 SCV000901819 uncertain significance Cardiomyopathy 2017-06-02 criteria provided, single submitter clinical testing
CSER_CC_NCGL; University of Washington Medical Center RCV000148690 SCV000190417 uncertain significance Primary familial hypertrophic cardiomyopathy 2014-06-01 no assertion criteria provided research

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