Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000697793 | SCV000826424 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2018-06-13 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with PMS2-related disease. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces leucine with proline at codon 718 of the PMS2 protein (p.Leu718Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. 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. 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. |
| Ambry Genetics | RCV001014609 | SCV001175336 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-27 | criteria provided, single submitter | clinical testing | The p.L718P variant (also known as c.2153T>C), located in coding exon 12 of the PMS2 gene, results from a T to C substitution at nucleotide position 2153. The leucine at codon 718 is replaced by proline, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Institute for Clinical Genetics, |
RCV002508250 | SCV002009104 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV002508250 | SCV002818091 | uncertain significance | not provided | 2022-07-01 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |