ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2300A>G (p.Lys767Arg)

gnomAD frequency: 0.00001  dbSNP: rs760786216
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000619049 SCV000740130 uncertain significance Cardiovascular phenotype 2024-10-07 criteria provided, single submitter clinical testing The p.K767R variant (also known as c.2300A>G), located in coding exon 23 of the MYBPC3 gene, results from an A to G substitution at nucleotide position 2300. The lysine at codon 767 is replaced by arginine, an amino acid with highly similar properties. This alteration has been reported in hypertrophic and dilated cardiomyopathy cohorts; however, clinical details were limited (Walsh R et al. Genet. Med. 2017;19:192-203; Trachoo O et al. PLoS One, 2022 Sep;17:e0267770). 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000629013 SCV000749923 uncertain significance Hypertrophic cardiomyopathy 2022-09-19 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 767 of the MYBPC3 protein (p.Lys767Arg). This variant is present in population databases (rs760786216, gnomAD 0.006%). This missense change has been observed in individuals with hyperthrophic cardiomyopathy and dilated cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 520345). 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 disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 RCV001190201 SCV001357643 uncertain significance Cardiomyopathy 2023-09-22 criteria provided, single submitter clinical testing This missense variant replaces lysine with arginine at codon 767 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 been reported in two individuals affected with hypertrophic cardiomyopathy and one individual affected with dilated cardiomyopathy (PMID: 27532257). This variant has been identified in 2/249182 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.
All of Us Research Program, National Institutes of Health RCV000629013 SCV004842366 uncertain significance Hypertrophic cardiomyopathy 2024-05-17 criteria provided, single submitter clinical testing This missense variant replaces lysine with arginine at codon 767 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 been reported in two individuals affected with hypertrophic cardiomyopathy and one individual affected with dilated cardiomyopathy (PMID: 27532257). This variant has been identified in 2/249182 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.
Clinical Genetics Laboratory, Skane University Hospital Lund RCV004696959 SCV005199326 uncertain significance not provided 2023-05-04 criteria provided, single submitter clinical testing

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