ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.1814A>G (p.Asp605Gly) (rs372371774)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000035440 SCV000059088 uncertain significance not specified 2012-02-09 criteria provided, single submitter clinical testing
GeneDx RCV000766341 SCV000208054 uncertain significance not provided 2018-04-27 criteria provided, single submitter clinical testing The D605G variant in the MYBPC3 gene has been reported previously in one individual with dilatedcardiomyopathy (DCM), however information regarding familial segregation was not reported, and in vitro functional studies were not performed (Hershberger et al., 2010). Furthermore, D605G has been reported as variant of uncertain significance by two other clinical laboratories (ClinVar SCV000059088.4; SCV000207044.1; Landrum et al., 2015). The D605G variant was not observed with any significant frequency in approximately 6,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. A variant in the same residue (D605N) has been reported in the Human Gene Mutation Database in association with cardiomyopathy, however D605N is classified as a variant of uncertain significance by GeneDx and by another clinical laboratory (Stenson et al., 2014; ClinVar SCV000059087.4; Landrum et al., 2015). D605G results in a non-conservative amino acid substitution at a position where amino acids with similar properties to Aspartic Acid are conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. In summary, D605G in the MYBPC3 gene is interpreted as a variant of uncertain significance.
Color RCV000777725 SCV000913671 uncertain significance Cardiomyopathy 2019-11-19 criteria provided, single submitter clinical testing
Agnes Ginges Centre for Molecular Cardiology,Centenary Institute RCV001089606 SCV001245080 uncertain significance Hypertrophic cardiomyopathy 2018-06-12 criteria provided, single submitter research This variant has been identified as part of our research program. Refer to the 'condition' field for the phenotype of the proband(s) identified with this variant. For further information please feel free to contact us.
Invitae RCV001089606 SCV001412629 uncertain significance Hypertrophic cardiomyopathy 2019-09-06 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 605 of the MYBPC3 protein (p.Asp605Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is present in population databases (rs372371774, ExAC 0.03%). This variant has been reported in an individual affected with familial dilated cardiomyopathy (PMID: 20215591). ClinVar contains an entry for this variant (Variation ID: 42573). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). 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.
Blueprint Genetics RCV000157309 SCV000207044 uncertain significance Primary dilated cardiomyopathy 2014-08-20 no assertion criteria provided clinical testing

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