Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000797150 | SCV000936693 | uncertain significance | not provided | 2023-08-25 | criteria provided, single submitter | clinical testing | 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: 643451). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. This variant is present in population databases (rs776035988, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 1066 of the MSH3 protein (p.Arg1066Ser). |
| Ambry Genetics | RCV002325520 | SCV002609697 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-26 | criteria provided, single submitter | clinical testing | The p.R1066S variant (also known as c.3198G>T), located in coding exon 23 of the MSH3 gene, results from a G to T substitution at nucleotide position 3198. The arginine at codon 1066 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Prevention |
RCV003424343 | SCV004118517 | uncertain significance | MSH3-related disorder | 2023-08-03 | criteria provided, single submitter | clinical testing | The MSH3 c.3198G>T variant is predicted to result in the amino acid substitution p.Arg1066Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 2 of ~251,000 alleles in gnomAD (http://gnomad.broadinstitute.org/variant/5-80169002-G-T). It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/643451/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Baylor Genetics | RCV003461094 | SCV004195170 | uncertain significance | Endometrial carcinoma | 2023-06-21 | criteria provided, single submitter | clinical testing |