ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2908C>T (p.Arg970Trp) (rs730880138)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001170192 SCV001332743 uncertain significance Cardiomyopathy 2018-01-30 criteria provided, single submitter clinical testing
Color Health, Inc RCV001170192 SCV001359095 uncertain significance Cardiomyopathy 2019-01-28 criteria provided, single submitter clinical testing
Invitae RCV001219625 SCV001391573 uncertain significance Hypertrophic cardiomyopathy 2020-02-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 970 of the MYBPC3 protein (p.Arg970Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs730880138, ExAC 0.01%). This variant has been observed in an individual affected with hypertrophic cardiomyopathy; however, this individual carried a different pathogenic MYBPC3 variant (PMID: 24111713). ClinVar contains an entry for this variant (Variation ID: 180411). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but 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.
GeneDx RCV001562532 SCV001785309 uncertain significance not provided 2019-04-22 criteria provided, single submitter clinical testing Reported in one Norwegian patient referred for HCM genetic testing who harbored a second nonsense variant in the MYBPC3 gene (Berge et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 33673806, 31589614, 24111713)
Blueprint Genetics RCV000157315 SCV000207050 likely pathogenic Primary familial hypertrophic cardiomyopathy 2014-04-11 no assertion criteria provided clinical testing

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