Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000584693 | SCV000690378 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-19 | criteria provided, single submitter | clinical testing | This missense variant replaces methionine with leucine at codon 1202 of the MSH6 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has been identified in 3/282820 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000587024 | SCV000695878 | uncertain significance | not provided | 2016-12-12 | criteria provided, single submitter | clinical testing | Variant summary: The MSH6 c.3604A>T (p.Met1202Leu) variant is located in the P-loop containing nucleoside triphosphate hydrolase and DNA mismatch repair protein MutS, C-terminal domains (via InterPro) and involves a conserved nucleotide. 5/5 in silico tools predict a benign outcome for this variant, although these predictions have yet to be functionally assessed. The variant of interest was not observed in the large and broad control populations from ExAC (0/121324 chromosomes). The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Therefore, until additional information becomes available (i.e., clinical and functional studies), the variant of interest has been classified as a "Variant of Uncertain Significance (VUS)." |
| Laboratory for Molecular Medicine, |
RCV000610333 | SCV000731396 | uncertain significance | not specified | 2017-03-06 | criteria provided, single submitter | clinical testing | The p.Met1202Leu variant in MSH6 has not been previously reported in individuals with Lynch syndrome and was absent from large population studies. Computational prediction tools and conservation analysis suggest that the p.Met1202Leu varian t may not impact the protein, though this information is not predictive enough t o rule out pathogenicity. In summary, the clinical significance of the p.Met1202 Leu variant is uncertain. |
| Invitae | RCV000629874 | SCV000750830 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2023-10-04 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000584693 | SCV002615054 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-14 | criteria provided, single submitter | clinical testing | The p.M1202L variant (also known as c.3604A>T), located in coding exon 7 of the MSH6 gene, results from an A to T substitution at nucleotide position 3604. The methionine at codon 1202 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |