ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.479G>A (p.Arg160Gln)

gnomAD frequency: 0.00004  dbSNP: rs730880617
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158283 SCV000208218 uncertain significance not provided 2020-04-09 criteria provided, single submitter clinical testing Reported in a 74-year-old individual who had several risk factors for cardiomyopathy (Bick et al., 2012); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 181037; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 22958901)
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV000627147 SCV000747972 uncertain significance Primary familial hypertrophic cardiomyopathy 2016-07-25 criteria provided, single submitter clinical testing
Invitae RCV001038326 SCV001201791 uncertain significance Hypertrophic cardiomyopathy 2023-07-14 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 160 of the MYBPC3 protein (p.Arg160Gln). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with risk factors for heart disease (PMID: 22958901). ClinVar contains an entry for this variant (Variation ID: 181037). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Color Diagnostics, LLC DBA Color Health RCV001180560 SCV001345518 uncertain significance Cardiomyopathy 2022-11-25 criteria provided, single submitter clinical testing This missense variant replaces arginine with glutamine at codon 160 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 3/204374 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.
Ambry Genetics RCV002336350 SCV002639553 uncertain significance Cardiovascular phenotype 2020-06-09 criteria provided, single submitter clinical testing The p.R160Q variant (also known as c.479G>A), located in coding exon 4 of the MYBPC3 gene, results from a G to A substitution at nucleotide position 479. The arginine at codon 160 is replaced by glutamine, an amino acid with highly similar properties. This variant has been reported in an individual from a community-based cohort with risk factors for cardiovascular disease (Bick AG et al. Am. J. Hum. Genet., 2012 Sep;91:513-9). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002478477 SCV002790057 uncertain significance Hypertrophic cardiomyopathy 4; Left ventricular noncompaction 10 2021-11-01 criteria provided, single submitter clinical testing

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