Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000236727 | SCV000292618 | uncertain significance | not provided | 2017-12-26 | criteria provided, single submitter | clinical testing | This variant is denoted MSH2 c.565G>A at the cDNA level, p.Ala189Thr (A189T) at the protein level, and results in the change of an Alanine to a Threonine (GCT>ACT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH2 Ala189Thr was not observed at a significant allele frequency in large population cohorts (Lek 2016). MSH2 Ala189Thr is located in the connector domain (L?tzen 2008, Kansikas 2011). In-silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether MSH2 Ala189Thr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Invitae | RCV000691636 | SCV000819422 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2019-12-04 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with threonine at codon 189 of the MSH2 protein (p.Ala189Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs63750821, ExAC 0.001%). This variant has not been reported in the literature in individuals with MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 245646). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000236727 | SCV000888223 | uncertain significance | not provided | 2018-05-04 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001024381 | SCV001186385 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-04 | criteria provided, single submitter | clinical testing | Insufficient evidence |