Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000212598 | SCV000149405 | uncertain significance | not provided | 2018-09-19 | criteria provided, single submitter | clinical testing | This variant is denoted MSH2 c.1182T>G at the cDNA level, p.Phe394Leu (F394L) at the protein level, and results in the change of a Phenylalanine to a Leucine (TTT>TTG). This variant was reported in an individual with familial and/or early-onset breast cancer (Jalkh 2017). MSH2 Phe394Leu was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located within the Lever domain and a region of interaction with MSH6 and MSH3 (Guerrette 1998, 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 Phe394Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Ambry Genetics | RCV000115496 | SCV000184289 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-27 | criteria provided, single submitter | clinical testing | Insufficient or conflicting evidence |
Invitae | RCV000477595 | SCV000548230 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2019-12-09 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with leucine at codon 394 of the MSH2 protein (p.Phe394Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is present in population databases (rs374135434, ExAC 0.003%). This variant has not been reported in the literature in individuals with MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 127627). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). 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 | RCV000115496 | SCV000684913 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-12-09 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000663103 | SCV000786218 | uncertain significance | Lynch syndrome I | 2018-03-23 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000212598 | SCV000884131 | uncertain significance | not provided | 2017-11-15 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000212598 | SCV001134330 | uncertain significance | not provided | 2019-04-19 | criteria provided, single submitter | clinical testing |