Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000814604 | SCV000955017 | pathogenic | not provided | 2024-12-12 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Phe326Leufs*3) in the MSH3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH3 are known to be pathogenic (PMID: 27476653, 37402566). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 657893). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (internal data). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV001019740 | SCV001181135 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-04-06 | criteria provided, single submitter | clinical testing | The c.978_984delTTCCCGG pathogenic mutation, located in coding exon 6 of the MSH3 gene, results from a deletion of 7 nucleotides at nucleotide positions 978 to 984, causing a translational frameshift with a predicted alternate stop codon (p.F326Lfs*3). This variant has been detected in conjunction with a MSH3 pathogenic variant in an individual with clinical features of MSH3-associated polyposis; however, the phase of the two variants is unknown (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Sema4, |
RCV001019740 | SCV002536560 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2021-12-08 | criteria provided, single submitter | curation | |
| Myriad Genetics, |
RCV003458544 | SCV004189061 | pathogenic | Familial adenomatous polyposis 4 | 2023-08-29 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Baylor Genetics | RCV003461226 | SCV004197087 | likely pathogenic | Endometrial carcinoma | 2023-09-12 | criteria provided, single submitter | clinical testing |