Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000811107 | SCV000951355 | pathogenic | not provided | 2025-01-23 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 17 of the MSH3 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or altered protein product. This variant is present in population databases (rs200639359, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with MSH3-related conditions. ClinVar contains an entry for this variant (Variation ID: 655023). Studies have shown that disruption of this splice site results in activation of a cryptic splice site, and produces a non-functional protein and/or introduces a premature termination codon (internal data). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV001015528 | SCV001176372 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2024-01-04 | criteria provided, single submitter | clinical testing | The c.2436-1G>A intronic variant results from a G to A substitution one nucleotide upstream from coding exon 18 of the MSH3 gene. Alterations that disrupt the canonical splice site are expected to result in aberrant splicing. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and may result in the creation or strengthening of a novel splice acceptor site. The resulting transcripts are predicted to be either: in-frame and not expected to trigger nonsense-mediated mRNA decay (direct evidence is unavailable) or out-of-frame and trigger nonsense-mediated mRNA decay. RNA studies have demonstrated that this alteration results in an incomplete splice defect; the clinical impact of this abnormal splicing is unknown at this time (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
Gene |
RCV000811107 | SCV004169649 | likely pathogenic | not provided | 2023-04-04 | criteria provided, single submitter | clinical testing | Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown.; Not observed at significant frequency in large population cohorts (gnomAD); Observed in at least one individual participating in a prospective elective genome sequencing study (Hou et al., 2020); This variant is associated with the following publications: (PMID: 31980526, 35366121) |
Myriad Genetics, |
RCV003458541 | SCV004189006 | likely pathogenic | Familial adenomatous polyposis 4 | 2023-08-30 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. mRNA analysis has demonstrated abnormal mRNA splicing occurs [Myriad internal data]. |
Baylor Genetics | RCV003467450 | SCV004197115 | uncertain significance | Endometrial carcinoma | 2024-02-28 | criteria provided, single submitter | clinical testing | |
Juno Genomics, |
RCV003458541 | SCV005415877 | likely pathogenic | Familial adenomatous polyposis 4 | criteria provided, single submitter | clinical testing | PM2_Supporting+PVS1 | |
Fulgent Genetics, |
RCV005036187 | SCV005666204 | likely pathogenic | Endometrial carcinoma; Familial adenomatous polyposis 4 | 2024-02-18 | criteria provided, single submitter | clinical testing |