Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001221997 | SCV001394076 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-06-11 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 950312). This variant has not been reported in the literature in individuals affected with MSH2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 574 of the MSH2 protein (p.Gln574Pro). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33357406) indicates that this missense variant is expected to disrupt MSH2 function. 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. |
Ambry Genetics | RCV002402680 | SCV002713635 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-09-05 | criteria provided, single submitter | clinical testing | The p.Q574P variant (also known as c.1721A>C), located in coding exon 11 of the MSH2 gene, results from an A to C substitution at nucleotide position 1721. The glutamine at codon 574 is replaced by proline, an amino acid with similar properties. 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 01;108:163-175). 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, |
RCV003449701 | SCV004186758 | likely pathogenic | Lynch syndrome 1 | 2023-08-03 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 33357406]. This variant is expected to disrupt protein structure [Myriad internal data]. |