Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000574877 | SCV000674236 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-29 | criteria provided, single submitter | clinical testing | The p.L257W variant (also known as c.770T>G), located in coding exon 7 of the PMS2 gene, results from a T to G substitution at nucleotide position 770. The leucine at codon 257 is replaced by tryptophan, 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. |
Invitae | RCV001371619 | SCV001568190 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-12-28 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 257 of the PMS2 protein (p.Leu257Trp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 486042). 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 expected to disrupt PMS2 protein function with a positive predictive value of 80%. 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. |
Gene |
RCV003222049 | SCV003918413 | uncertain significance | not provided | 2023-04-07 | criteria provided, single submitter | clinical testing | 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; This variant is associated with the following publications: (PMID: 11574484) |
Baylor Genetics | RCV003459392 | SCV004207827 | uncertain significance | Lynch syndrome 4 | 2023-05-28 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000574877 | SCV004359658 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-06 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with tryptophan at codon 257 of the PMS2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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. |
All of Us Research Program, |
RCV004001124 | SCV004822830 | uncertain significance | Lynch syndrome | 2023-04-03 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with tryptophan at codon 257 of the PMS2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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. |