ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.1226+6T>C

gnomAD frequency: 0.00015  dbSNP: rs397515892
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Total submissions: 5
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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 RCV000035377 SCV000059025 uncertain significance not specified 2010-03-16 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000462404 SCV000546479 uncertain significance Hypertrophic cardiomyopathy 2023-12-12 criteria provided, single submitter clinical testing This sequence change falls in intron 14 of the MYBPC3 gene. It does not directly change the encoded amino acid sequence of the MYBPC3 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs397515892, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This variant has been observed in individual(s) with dilated cardiomyopathy (PMID: 30871747). ClinVar contains an entry for this variant (Variation ID: 42512). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant does not affect mRNA splicing (PMID: 28679633). 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 RCV001188891 SCV001356064 uncertain significance Cardiomyopathy 2023-02-15 criteria provided, single submitter clinical testing This variant causes a T>C nucleotide substitution at the +6 position of intron 14 of the MYBPC3 gene. Splice site prediction tools and conservation analysis are inconclusive regarding the impact of this variant on RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with dilated cardiomyopathy (PMID: 30871747, 31179125) and in a case of sudden cardiac death (PMID: 36293497). This variant has been identified in 23/241524 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 RCV001778673 SCV002015816 likely benign not provided 2021-05-11 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 28679633, 30871747)
All of Us Research Program, National Institutes of Health RCV000462404 SCV004819798 uncertain significance Hypertrophic cardiomyopathy 2023-11-30 criteria provided, single submitter clinical testing This variant causes a T>C nucleotide substitution at the +6 position of intron 14 of the MYBPC3 gene. Splice site prediction tools and conservation analysis are inconclusive regarding the impact of this variant on RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with dilated cardiomyopathy (PMID: 30871747, 31179125) and in a case of sudden cardiac death (PMID: 36293497). This variant has been identified in 23/241524 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.

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