ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.927-1G>C

dbSNP: rs2095894178
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Agnes Ginges Centre for Molecular Cardiology, Centenary Institute RCV005054326 SCV001245085 likely pathogenic Hypertrophic cardiomyopathy 4 2018-11-14 criteria provided, single submitter research MYBPC3 c.927-1G>C has not been previously reported and is absent in the Genome Aggregation Database (http://gnomad.broadinstitute.org/). We identified this variant in a proband diagnosed with HCM. Based on the adapted ACMG guidelines (Kelly MA, et al., 2018), this variant results in loss of function of MYBPC3 (PVS1) and is rare in the general population (PM2), therefore we classify MYBPC3 c.927-1G>C as 'likely pathogenic'.
All of Us Research Program, National Institutes of Health RCV001089611 SCV004840102 pathogenic Hypertrophic cardiomyopathy 2023-12-10 criteria provided, single submitter clinical testing The c.927-1G>C variant of the MYBPC3 gene affects the acceptor splice site in intron 11. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547). Loss-of-function variants in MYBPC3 are known to be pathogenic (PMID: 19574547). Disruption of this splice site, caused by variant c.927-2A>G, has been observed in individuals with hypertrophic cardiomyopathy (PMID: 9562578, 22574137, 25078086, 27532257), and has been interpreted as pathogenic (ClinVar ID:42806). In addition, the c.927-1G>C variant is absent in the general population by the gnomAD database. Based on the available evidence, c.927-1G>C variant of the MYBPC3 gene is classified as pathogenic.
Color Diagnostics, LLC DBA Color Health RCV005402969 SCV006064383 likely pathogenic Cardiomyopathy 2024-03-06 criteria provided, single submitter clinical testing This variant causes a G>C nucleotide substitution at the canonical -1 position of intron 11 of the MYBPC3 gene. Splice site prediction tools suggest that this variant may have a significant impact on RNA splicing. Although this prediction has not been confirmed in published RNA studies, this variant is expected to result in an absent or disrupted protein product. This variant has been reported in at least one individual affected with hypertrophic cardiomyopathy (PMID: 32841044, 37821546). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). A different variant affecting the same splice donor site, c.927-2A>G, is known to be disease-causing (ClinVar variation ID: 42806). Loss of MYBPC3 function is a known mechanism of disease. Based on the available evidence, this variant is classified as Likely Pathogenic.

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