Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000122987 | SCV000166275 | uncertain significance | Hereditary nonpolyposis colon cancer | 2018-09-06 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with arginine at codon 872 of the MSH2 protein (p.Lys872Arg). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and arginine. The frequency data for this variant (rs587780686) in the population databases is unreliable, as metrics indicate poor quality at this position in the ExAC database. This variant has been reported in an individual affected with ovarian cancer (PMID: 23047549), and an individual affected with pancreatic cancer (PMID: 26483394). CinVar contains an entry for this variant (Variation ID: 135859). 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 tolerated, but these predictions have not been confirmed by published functional studies. 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. |
| Counsyl | RCV000411448 | SCV000488337 | uncertain significance | Lynch syndrome I | 2016-03-01 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000563636 | SCV000669775 | likely benign | Hereditary cancer-predisposing syndrome | 2016-03-30 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: In silico models in agreement (benign),Other strong data supporting benign classification |