Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000705298 | SCV000834288 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2021-07-15 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with cysteine at codon 358 of the PMS2 protein (p.Ser358Cys). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and cysteine. This variant is present in population databases (rs762299041, ExAC 0.001%). 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 disruptive, 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. |
Color Diagnostics, |
RCV003584728 | SCV004359637 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-07 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with cysteine at codon 358 of the PMS2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251224 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. |