ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2909G>A (p.Arg970Gln) (rs727504346)

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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 RCV000154467 SCV000204136 uncertain significance not specified 2014-07-03 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Arg970Gln varia nt in MYBPC3 has been identified by our laboratory in 1 Caucasian adult with DCM (Pugh 2014, this individual's relative). Data from large studies is insufficien t to assess its frequency in the general population. Arginine (Arg) at position 970 is not completely conserved in evolution, and one species (American alligato r) has the variant amino acid (Gln) at this position, raising the possibility th at this change may be tolerated. This variant was also predicted to be benign us ing a computational tool clinically validated by our laboratory. This tool's ben ign prediction is estimated to be correct 89% of the time (Jordan 2011). In summ ary, the clinical significance of the Arg970Gln variant is uncertain.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724501 SCV000228595 uncertain significance not provided 2015-02-19 criteria provided, single submitter clinical testing
Invitae RCV000462920 SCV000546442 uncertain significance Hypertrophic cardiomyopathy 2018-11-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 970 of the MYBPC3 protein (p.Arg970Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs727504346, ExAC 0.007%). This variant has been observed in individuals affected with dilated cardiomyopathy or hypertrophic cardiomyopathy (PMID: 22464770, 27532257, 28640247). ClinVar contains an entry for this variant (Variation ID: 177832). 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.
Ambry Genetics RCV000617862 SCV000737381 uncertain significance Cardiovascular phenotype 2017-01-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000777993 SCV000914099 uncertain significance Cardiomyopathy 2018-09-24 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the MYBPC3 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact the RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in an individual affected with dilated cardiomyopathy (PMID: 22464770) and in an individual affected with hypertrophic cardiomyopathy (PMID: 27532257). This variant has been identified in 11/211144 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Stanford Center for Inherited Cardiovascular Disease,Stanford University RCV000724501 SCV000925164 uncertain significance not provided 2018-02-02 no assertion criteria provided provider interpretation

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