Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002229165 | SCV000260162 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2021-08-03 | criteria provided, single submitter | clinical testing | In summary, this variant is a rare 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. 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. This variant is present in population databases (rs755348833, ExAC <0.01%) but has not been reported in the literature in individuals with a PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 219964). This sequence change replaces threonine with isoleucine at codon 458 of the PMS2 protein (p.Thr458Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. |
Gene |
RCV002469067 | SCV002765506 | uncertain significance | not provided | 2022-06-17 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |