Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000807040 | SCV000947068 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2019-05-18 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 (ExAC) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. This sequence change replaces leucine with phenylalanine at codon 770 of the PMS2 protein (p.Leu770Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. |
| Ambry Genetics | RCV002442697 | SCV002734929 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-27 | criteria provided, single submitter | clinical testing | The p.L770F variant (also known as c.2310G>T), located in coding exon 14 of the PMS2 gene, results from a G to T substitution at nucleotide position 2310. The leucine at codon 770 is replaced by phenylalanine, an amino acid with highly 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. |
| Genetic Services Laboratory, |
RCV003151154 | SCV003839893 | uncertain significance | not specified | 2022-07-18 | no assertion criteria provided | clinical testing | DNA sequence analysis of the PMS2 gene demonstrated a sequence change, c.2310G>T, in exon 14 that results in an amino acid change, p.Leu770Phe. This sequence change does not appear to have been previously described in individuals with PMS2-related disorders and has also not been described in population databases such as ExAC and gnomAD. The p.Leu770Phe change affects a highly conserved amino acid residue located in a domain of the PMS2 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Leu770Phe substitution. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Leu770Phe change remains unknown at this time. |