ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2177G>A (p.Arg726His)

gnomAD frequency: 0.00004  dbSNP: rs397515953
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Total submissions: 4
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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 RCV000035471 SCV000059119 uncertain significance not specified 2012-09-26 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Arg726His varia nt in MYBPC3 has not been reported in the literature nor previously identified b y our laboratory. The affected amino acid is poorly conserved in evolution with the variant amino acid (His) present in several mammalian species. This sugges ts (but does not prove) that this change is tolerated. This variant is less like ly disease causing but additional data is needed to confidently rule out a role in disease.
Color Diagnostics, LLC DBA Color Health RCV001185550 SCV001351799 uncertain significance Cardiomyopathy 2023-09-27 criteria provided, single submitter clinical testing This missense variant replaces arginine with histidine at codon 726 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 not been reported in individuals affected with MYBPC3-related disorders in the literature. This variant has been identified in 7/279060 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.
Invitae RCV001235345 SCV001408026 uncertain significance Hypertrophic cardiomyopathy 2023-11-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 726 of the MYBPC3 protein (p.Arg726His). This variant is present in population databases (rs397515953, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 42603). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV001839482 SCV002099710 uncertain significance not provided 2022-12-09 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function

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