ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.292+1G>A

dbSNP: rs1433492944
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002001519 SCV002273734 likely pathogenic Hypertrophic cardiomyopathy 2023-12-14 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 2 of the MYBPC3 gene. 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), and loss-of-function variants in MYBPC3 are known to be pathogenic (PMID: 19574547). This variant is not present in population databases (gnomAD no frequency). 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: 1489518). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV003150475 SCV003838290 likely pathogenic Cardiomyopathy 2022-05-18 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV003339874 SCV004047803 uncertain significance Hypertrophic cardiomyopathy 4 criteria provided, single submitter clinical testing The splice site variant c.292+1G>A in MYBPC3 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is novel (not in any individuals) in 1000 Genomes and allele frequency of 0.000006253 is reported in gnomAD . The nucleotide change in MYBPC3 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates.For these reasons, this variant has been classified as Uncertain Significance.

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