ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2002C>T (p.Arg668Cys)

gnomAD frequency: 0.00001  dbSNP: rs730880561
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001176411 SCV001340387 uncertain significance Cardiomyopathy 2023-03-23 criteria provided, single submitter clinical testing This missense variant replaces arginine with cysteine at codon 668 of the MYBPC3 protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in at least one individual affected with hypertrophic cardiomyopathy (PMID: 21302287, 32481709). This variant has been identified in 4/280494 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001176411 SCV002042152 uncertain significance Cardiomyopathy 2020-06-09 criteria provided, single submitter clinical testing
AiLife Diagnostics, AiLife Diagnostics RCV002223798 SCV002502022 uncertain significance not provided 2022-02-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV003298178 SCV003989420 uncertain significance Cardiovascular phenotype 2023-06-05 criteria provided, single submitter clinical testing The p.R668C variant (also known as c.2002C>T), located in coding exon 21 of the MYBPC3 gene, results from a C to T substitution at nucleotide position 2002. The arginine at codon 668 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in hypertrophic cardiomyopathy (HCM) cohorts (Roncarati R et al. J Cell Physiol, 2011 Nov;226:2894-900; Mazzarotto F et al. Genet Med, 2019 Feb;21:284-292; Magrì D et al. J Clin Med, 2020 May;9:[ePub ahead of print]). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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