ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3799C>T (p.Arg1267Cys)

gnomAD frequency: 0.00005  dbSNP: rs765825263
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000462292 SCV000546436 uncertain significance Hypertrophic cardiomyopathy 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1267 of the MYBPC3 protein (p.Arg1267Cys). This variant is present in population databases (rs765825263, 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: 407316). 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 RCV001176814 SCV001340873 uncertain significance Cardiomyopathy 2023-01-27 criteria provided, single submitter clinical testing This missense variant replaces arginine with cysteine at codon 1267 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 6/278688 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.
GeneDx RCV001764391 SCV001990416 uncertain significance not provided 2022-08-03 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002356670 SCV002622724 uncertain significance Cardiovascular phenotype 2021-07-01 criteria provided, single submitter clinical testing The p.R1267C variant (also known as c.3799C>T), located in coding exon 33 of the MYBPC3 gene, results from a C to T substitution at nucleotide position 3799. The arginine at codon 1267 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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.
Fulgent Genetics, Fulgent Genetics RCV002506116 SCV002814161 uncertain significance Hypertrophic cardiomyopathy 4; Left ventricular noncompaction 10 2021-10-14 criteria provided, single submitter clinical testing

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