Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000621634 | SCV000740232 | pathogenic | Cardiovascular phenotype | 2017-11-13 | criteria provided, single submitter | clinical testing | The c.505_505+7delGGTGAGTG pathogenic mutation results from a deletion of GGTGAGTG at nucleotide positions 505 to 505+7, spanning the last nucleotide to the seven nucleotides downstream of coding exon four of the MYBPC3 gene. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation. |
Invitae | RCV003748266 | SCV004503410 | likely pathogenic | Hypertrophic cardiomyopathy | 2023-12-24 | criteria provided, single submitter | clinical testing | This variant results in the deletion of part of exon 4 (c.505_505+7del) 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: 520377). 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. |