Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000470673 | SCV000551928 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2019-04-23 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with asparagine at codon 238 of the PMS2 protein (p.Ser238Asn). The serine residue is moderately conserved and there is a small physicochemical difference between serine and asparagine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a PMS2-related disease. 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, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV000569996 | SCV000664904 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-04-07 | criteria provided, single submitter | clinical testing | Insufficient or conflicting evidence |
Color | RCV000569996 | SCV000910191 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-11-19 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000987844 | SCV001137316 | likely benign | Hereditary nonpolyposis colorectal cancer type 4 | 2019-05-28 | criteria provided, single submitter | clinical testing |