Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000167210 | SCV000218047 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-02-27 | criteria provided, single submitter | clinical testing | The p.V31L variant (also known as c.91G>T), located in coding exon 2 of the PMS2 gene, results from a G to T substitution at nucleotide position 91. The valine at codon 31 is replaced by leucine, 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. |
Color Diagnostics, |
RCV000167210 | SCV000691127 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-05 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with leucine at codon 31 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 PMS2-related disorders in the literature. 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. |
Invitae | RCV000792431 | SCV000931729 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2021-08-24 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PMS2 protein function. ClinVar contains an entry for this variant (Variation ID: 187477). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This sequence change replaces valine with leucine at codon 31 of the PMS2 protein (p.Val31Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. |
Sema4, |
RCV000167210 | SCV002530403 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-24 | criteria provided, single submitter | curation | |
Preventiongenetics, |
RCV003390874 | SCV004110278 | uncertain significance | PMS2-related condition | 2023-04-05 | criteria provided, single submitter | clinical testing | The PMS2 c.91G>T variant is predicted to result in the amino acid substitution p.Val31Leu. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/187477/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Baylor Genetics | RCV003462237 | SCV004205400 | uncertain significance | Lynch syndrome 4 | 2023-10-10 | criteria provided, single submitter | clinical testing |