Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000688719 | SCV000816342 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2018-12-06 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 41712). The frequency data for this variant in the population databases (rs200629542, ExAC) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. This sequence change replaces proline with leucine at codon 800 of the PMS2 protein (p.Pro800Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. 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 | RCV003298041 | SCV004005572 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-21 | criteria provided, single submitter | clinical testing | The p.P800L variant (also known as c.2399C>T), located in coding exon 14 of the PMS2 gene, results from a C to T substitution at nucleotide position 2399. The proline at codon 800 is replaced by leucine, 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. |
Biesecker Lab/Clinical Genomics Section, |
RCV000034627 | SCV000043414 | variant of unknown significance | not provided | 2012-07-13 | no assertion criteria provided | research | Converted during submission to Uncertain significance. |