Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000228716 | SCV000285082 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2018-03-12 | criteria provided, single submitter | clinical testing | 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. 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 and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 237892). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 568 of the PMS2 protein (p.Pro568Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. |
All of Us Research Program, |
RCV003998789 | SCV004824477 | uncertain significance | Lynch syndrome | 2023-06-26 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with leucine at codon 568 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PMS2-related disorders in the literature. This variant has been identified in 1/251372 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |