Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588121 | SCV000696271 | uncertain significance | not provided | 2016-11-10 | criteria provided, single submitter | clinical testing | Variant summary: The c.478C>A (p.Gln160Lys) in MSH2 gene is a missense change that involves a non-conserved nucleotide and 5/5 in silico tools predict benign outcome. The variant of interest is located within a region that has a high homology to the connector domain of DNA mismatch repair proteins. The functional impact of this missense change is yet to be studied. The variant is absent from the large control population dataset of ExAC and has not, to our knowledge, been reported in the affected individuals via published reports or reputable databases/clinical laboratories. The variant was found to co-occur with a Likely Pathogenic mutation, c.349A>G (p.R117G0 in CHEK2 gene in an internal sample. At this time there is not sufficient undeniable evidence to classify this variant with confidence. Taken together, the variant was classified as VUS until more data becomes available. |
All of Us Research Program, |
RCV004002417 | SCV004827757 | uncertain significance | Lynch syndrome | 2023-06-08 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with lysine at codon 160 of the MSH2 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 MSH2-related disorders in the literature. This variant has not been identified 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. |