Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000158319 | SCV000208254 | pathogenic | not provided | 2022-04-01 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Published functional study demonstrates a damaging effect by activation of a cryptic splice site and produces a frameshift and eventual protein truncation in exon 12 (Frank-Hansen et al., 2008); This variant is associated with the following publications: (PMID: 19574547, 29493010, 29998127, 24704860, 28771489, 18337725) |
Invitae | RCV001040124 | SCV001203684 | pathogenic | Hypertrophic cardiomyopathy | 2023-03-02 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 9 of the MYBPC3 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs587776700, gnomAD 0.0009%). Disruption of this splice site has been observed in individuals with hypertrophic cardiomyoapthy and/or hypertrophic cardiomyopathy (PMID: 18337725; Invitae). ClinVar contains an entry for this variant (Variation ID: 8619). Studies have shown that disruption of this splice site results in activates a cryptic splice site resulting in a 34 nt intron inclusion. and introduces a premature termination codon (PMID: 18337725). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |
CHEO Genetics Diagnostic Laboratory, |
RCV001797997 | SCV002042237 | pathogenic | Cardiomyopathy | 2022-04-29 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000009150 | SCV000029367 | pathogenic | Hypertrophic cardiomyopathy 4 | 2008-09-01 | no assertion criteria provided | literature only |