Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000573656 | SCV000664899 | likely benign | Hereditary cancer-predisposing syndrome | 2017-06-06 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: Other strong data supporting benign classification,In silico models in agreement (benign) |
| Color | RCV000573656 | SCV000903920 | likely benign | Hereditary cancer-predisposing syndrome | 2016-08-06 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000464024 | SCV000551927 | uncertain significance | Hereditary nonpolyposis colon cancer | 2018-10-31 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with serine at codon 497 of the PMS2 protein (p.Gly497Ser). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs749826312, ExAC 0.01%). This variant has not been reported in the literature in individuals with a PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 411016). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on PMS2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |