Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001237221 | SCV001409973 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2023-07-07 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002447183 | SCV002611911 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-05 | criteria provided, single submitter | clinical testing | The p.D379Y variant (also known as c.1135G>T), located in coding exon 7 of the MSH2 gene, results from a G to T substitution at nucleotide position 1135. The aspartic acid at codon 379 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| All of Us Research Program, |
RCV004004870 | SCV004827165 | uncertain significance | Lynch syndrome | 2023-08-15 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with tyrosine at codon 379 of the MSH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251432 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. |