Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| University of Washington Department of Laboratory Medicine, |
RCV000758655 | SCV000887420 | likely benign | Lynch syndrome | 2018-05-01 | criteria provided, single submitter | clinical testing | MSH2 NM_000251.2:c.2095T>C has a 2.2% probability of pathogenicity based on combining prior probability from public data with a likelihood ratio of 0.20 to 1, generated from evidence of seeing this as a somatic mutation in a tumor without loss of heterozygosity at the MSH2 locus. See Shirts et al 2018, PMID 29887214. |
| Ambry Genetics | RCV004027161 | SCV005033545 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-02 | criteria provided, single submitter | clinical testing | The p.S699P variant (also known as c.2095T>C), located in coding exon 13 of the MSH2 gene, results from a T to C substitution at nucleotide position 2095. The serine at codon 699 is replaced by proline, an amino acid with similar properties. Using a Bayesian analysis that incorporates tumor mutation data, this variant was classified as likely benign (Shirts BH et al. Am J Hum Genet, 2018 Jul;103:19-29). However, in a massively parallel cell-based functional assay testing susceptibility to a DNA damaging agent, 6-thioguanine (6-TG), this variant was reported to be functionally deleterious (Jia X et al. Am J Hum Genet, 2021 Jan;108:163-175). This amino acid position is not well 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. |