Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000798020 | SCV000937612 | uncertain significance | not provided | 2024-12-30 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 149 of the MSH3 protein (p.Ser149Asn). This variant is present in population databases (no rsID available, gnomAD 0.004%). 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: 644161). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002332607 | SCV002636667 | likely benign | Hereditary cancer-predisposing syndrome | 2020-03-28 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Fulgent Genetics, |
RCV005036151 | SCV005673165 | uncertain significance | Endometrial carcinoma; Familial adenomatous polyposis 4 | 2024-05-01 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004751710 | SCV005356777 | uncertain significance | MSH3-related disorder | 2024-07-29 | no assertion criteria provided | clinical testing | The MSH3 c.446G>A variant is predicted to result in the amino acid substitution p.Ser149Asn. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0046% of alleles in individuals of European (Finnish) descent in gnomAD and has conflicting interpretations of pathogenicity in ClinVar ranging from likely benign to uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/644161/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |