ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3227A>G (p.Asp1076Gly)

gnomAD frequency: 0.00001  dbSNP: rs730880140
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001564140 SCV001787253 uncertain significance not provided 2020-09-23 criteria provided, single submitter clinical testing Reported in association with cardiomyopathy (Dal Ferro et al., 2017); however, additional clinical information was not provided; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33673806, 28416588, 31514951)
Labcorp Genetics (formerly Invitae), Labcorp RCV001850183 SCV002157542 uncertain significance Hypertrophic cardiomyopathy 2021-03-28 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 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 C15"). This variant has been observed in individual(s) with dilated cardiomyopathy (PMID: 28416588, 31514951). ClinVar contains an entry for this variant (Variation ID: 180413). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glycine at codon 1076 of the MYBPC3 protein (p.Asp1076Gly). The aspartic acid residue is weakly conserved and there is a moderate physicochemical difference between aspartic acid and glycine.
All of Us Research Program, National Institutes of Health RCV001850183 SCV004832081 uncertain significance Hypertrophic cardiomyopathy 2023-06-08 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glycine at codon 1076 of the MYBPC3 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in at least one individual affected with dilated cardiomyopathy (PMID: 28416588, 31514951) and in an individual suspected to be affected with hypertrophic cardiomyopathy (PMID: 33673806). This variant has been identified in 1/31354 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Blueprint Genetics RCV000157317 SCV000207052 likely pathogenic Primary dilated cardiomyopathy; Primary familial hypertrophic cardiomyopathy 2014-09-29 no assertion criteria provided clinical testing

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