Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000160609 | SCV000211206 | uncertain significance | not provided | 2018-04-12 | criteria provided, single submitter | clinical testing | This variant is denoted MSH2 c.2288C>T at the cDNA level, p.Ala763Val (A763V) at the protein level, and results in the change of an Alanine to a Valine (GCA>GTA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH2 Ala763Val was not observed in large population cohorts (Lek 2016). This variant is located in the ATPase 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 Ala763Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Ambry Genetics | RCV000218725 | SCV000273937 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-12 | criteria provided, single submitter | clinical testing | Insufficient or conflicting evidence |
Invitae | RCV000456427 | SCV000548276 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2019-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with valine at codon 763 of the MSH2 protein (p.Ala763Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 182578). 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. |
Color | RCV000218725 | SCV000904007 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-12 | criteria provided, single submitter | clinical testing |