Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000129574 | SCV000184356 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-06-29 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: Insufficient evidence |
Invitae | RCV000473039 | SCV000548198 | uncertain significance | Hereditary nonpolyposis colon cancer | 2018-11-15 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with aspartic acid at codon 606 of the MSH2 protein (p.Val606Asp). The valine residue is moderately conserved and there is a large physicochemical difference between valine and aspartic acid. This variant is present in population databases (rs376044376, 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: 141180). 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: "Probably Damaging"; 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. |