ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.917G>A (p.Arg306Gln)

gnomAD frequency: 0.00002  dbSNP: rs373204728
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000035678 SCV000059329 uncertain significance not specified 2014-02-11 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Arg306Gln varia nt in MYBPC3 has now been identified by our laboratory in one individual with DC M and one individual with HCM. It has also been identified in 1/4036 African Am erican chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washingt on.edu). Arginine (Arg) at position 306 is not evolutionarily conserved and the change to glutamine (Gln) was predicted to be benign using a computational tool clinically validated by our laboratory. This tool's benign prediction is estimat ed to be correct 89% of the time (Jordan 2011). Although these data support that the Arg306Gln variant is more likely benign, additional information is needed t o fully assess the clinical significance of this variant.
GeneDx RCV000766317 SCV000208255 uncertain significance not provided 2023-04-26 criteria provided, single submitter clinical testing Identified in a patient with cardiomyopathy in published literature (Walsh et al., 2017); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27532257, 31983221)
Invitae RCV001065634 SCV001230602 uncertain significance Hypertrophic cardiomyopathy 2022-08-09 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 306 of the MYBPC3 protein (p.Arg306Gln). This variant is present in population databases (rs373204728, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of dilated cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 42802). 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 tolerated. 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.

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