Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001014350 | SCV001175048 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2024-06-27 | criteria provided, single submitter | clinical testing | The p.C693Y variant (also known as c.2078G>A), located in coding exon 13 of the MSH2 gene, results from a G to A substitution at nucleotide position 2078. The cysteine at codon 693 is replaced by tyrosine, an amino acid with highly dissimilar properties. This variant has been identified in multiple probands with Lynch syndrome-associated tumors; several who met Amsterdam I/II criteria for Lynch syndrome (Rossi BM et al. BMC Cancer, 2017 Sep;17:623; Schneider NB et al. Cancer Med, 2018 05;7:2078-2088; Soares BL et al. Fam Cancer, 2018 Jul;17:387-394; Zhunussova G et al. Front Oncol, 2019 Aug;9:673). Based on internal structural analysis, p.C693Y is deleterious (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Myriad Genetics, |
RCV003449101 | SCV004186647 | likely pathogenic | Lynch syndrome 1 | 2023-08-07 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [Myriad internal data]. This variant is expected to disrupt protein structure [Myriad internal data]. |
| Genetic Laboratory, |
RCV000445396 | SCV000537128 | uncertain significance | not specified | 2016-01-11 | no assertion criteria provided | research |