Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000629916 | SCV000750872 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2021-03-12 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with MSH2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with glutamic acid at codon 348 of the MSH2 protein (p.Gln348Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. 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 | RCV002395656 | SCV002708197 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-13 | criteria provided, single submitter | clinical testing | The p.Q348E variant (also known as c.1042C>G), located in coding exon 6 of the MSH2 gene, results from a C to G substitution at nucleotide position 1042. The glutamine at codon 348 is replaced by glutamic acid, an amino acid with highly similar 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, |
RCV004002781 | SCV004830564 | uncertain significance | Lynch syndrome | 2023-04-27 | criteria provided, single submitter | clinical testing |