Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000630171 | SCV000751127 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2017-10-31 | 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been reported in an individual affected with lynch syndrome (PMID: 23837913). This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with proline at codon 156 of the PMS2 protein (p.Thr156Pro). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and proline. |
Color Diagnostics, |
RCV003584682 | SCV004359680 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-08 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with proline at codon 156 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 been reported in an individual affected with colorectal cancer that exhibited loss of PMS2 protein by immunohistochemistry analyses (PMID: 23837913). This variant has not been identified 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. |