Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000565456 | SCV000662225 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-06-17 | criteria provided, single submitter | clinical testing | Insufficient or conflicting evidence |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000759112 | SCV000888218 | uncertain significance | not provided | 2018-05-17 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000793685 | SCV000933050 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2018-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with alanine at codon 756 of the MSH2 protein (p.Thr756Ala). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs750646335, ExAC 0.01%). This variant has not been reported in the literature in individuals with MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 479790). 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. 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. |