Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001385720 | SCV001585682 | pathogenic | not provided | 2024-11-04 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln917*) 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 not present in population databases (gnomAD no frequency). 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: 1072876). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002438890 | SCV002747560 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-08-18 | criteria provided, single submitter | clinical testing | The p.Q917* pathogenic mutation (also known as c.2749C>T), located in coding exon 20 of the MSH3 gene, results from a C to T substitution at nucleotide position 2749. This changes the amino acid from a glutamine to a stop codon within coding exon 20. 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. |
| Myriad Genetics, |
RCV003458691 | SCV004189142 | pathogenic | Familial adenomatous polyposis 4 | 2023-08-31 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |
| St. |
RCV003458691 | SCV005689140 | uncertain significance | Familial adenomatous polyposis 4 | 2024-08-05 | criteria provided, single submitter | clinical testing | The MSH3 c.2749C>T (p.Gln917Ter) change is a nonsense variant that is predicted to cause premature protein truncation and loss of normal protein function. This variant is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). To our knowledge, this variant has not been reported in the literature in individuals with MSH3-associated polyposis syndrome, however downstream loss of function variants have been reported (PMID: 27476653). In summary, this variant meets criteria to be classified as pathogenic. |