ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2905+1G>C

dbSNP: rs397515991
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000035538 SCV000059188 pathogenic Hypertrophic cardiomyopathy 2012-08-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000035538 SCV005836078 pathogenic Hypertrophic cardiomyopathy 2024-05-26 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 27 of the MYBPC3 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with hypertrophic cardiomyopathy (PMID: 21302287, 21959974, 30550750). ClinVar contains an entry for this variant (Variation ID: 42667). Studies have shown that disruption of this splice site results in skipping of exon 27, but is expected to preserve the integrity of the reading-frame (PMID: 11499719, 25031304). For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health RCV005402812 SCV006064797 pathogenic Cardiomyopathy 2024-03-12 criteria provided, single submitter clinical testing This variant causes a G>C nucleotide substitution at the canonical +1 position of intron 27 of the MYBPC3 gene. Splice site prediction tools predict 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: 25611685, 27532257, 33495597). 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.2905+1G>A, is known to be disease-causing (ClinVar variation ID: 42666). Loss of MYBPC3 function is a known mechanism of disease. Based on the available evidence, this variant is classified as Pathogenic.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV005403736 SCV006066175 pathogenic Cardiovascular phenotype 2024-11-06 criteria provided, single submitter clinical testing PVS1, PM2, PS4_supp

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