Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001384173 | SCV001583559 | pathogenic | not provided | 2024-07-01 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp562*) 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: 1071655). For these reasons, this variant has been classified as Pathogenic. |
| Myriad Genetics, |
RCV003458686 | SCV004189135 | pathogenic | Familial adenomatous polyposis 4 | 2023-08-30 | 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. |
| Baylor Genetics | RCV003469704 | SCV004195108 | likely pathogenic | Endometrial carcinoma | 2023-08-20 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001384173 | SCV004221047 | likely pathogenic | not provided | 2022-12-03 | criteria provided, single submitter | clinical testing | This nonsense variant is predicted to cause the premature termination of MSH3 protein synthesis. The variant has not been reported in individuals with MSH3-related diseases in the published literature. The frequency of this variant in the general population, 0.000004 (1/250564 chromosomes, http://gnomad.broadinstitute.org), is consistent with pathogenicity. Based on the available information, this variant is classified as likely pathogenic. |
| Ambry Genetics | RCV004945108 | SCV005448331 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-11-05 | criteria provided, single submitter | clinical testing | The p.W562* pathogenic mutation (also known as c.1686G>A), located in coding exon 12 of the MSH3 gene, results from a G to A substitution at nucleotide position 1686. This changes the amino acid from a tryptophan to a stop codon within coding exon 12. 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. |