Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000214892 | SCV000275685 | uncertain significance | Hereditary cancer-predisposing syndrome | 2025-02-19 | criteria provided, single submitter | clinical testing | The p.Q205H variant (also known as c.615G>T), located in coding exon 6 of the PMS2 gene, results from a G to T substitution at nucleotide position 615. The glutamine at codon 205 is replaced by histidine, an amino acid with highly similar properties. This variant has been reported in an individual with colon cancer (AlHarbi M et al. Oncotarget, 2023 Jun;14:580-594). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
Labcorp Genetics |
RCV000468010 | SCV000552005 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2025-01-12 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001284679 | SCV000565386 | uncertain significance | not provided | 2022-12-09 | 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) |
Color Diagnostics, |
RCV000214892 | SCV000686221 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-14 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with histidine at codon 205 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 been identified in 5/251494 chromosomes in the general population by the Genome Aggregation Database (gnomAD). A different variant affecting the same codon, c.614A>C (p.Gln205Pro), is considered to be disease-causing (ClinVar variation ID: 91361), suggesting that Gln at this position is important for the protein function. 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001284679 | SCV001470603 | uncertain significance | not provided | 2020-02-21 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV003997922 | SCV004839951 | uncertain significance | Lynch syndrome | 2024-08-30 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with histidine at codon 205 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 been identified in 5/251494 chromosomes in the general population by the Genome Aggregation Database (gnomAD). A different variant affecting the same codon, c.614A>C (p.Gln205Pro), is considered to be disease-causing (ClinVar variation ID: 91361), suggesting that Gln at this position is important for the protein function. 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. |
Baylor Genetics | RCV004567573 | SCV005056404 | uncertain significance | Lynch syndrome 4 | 2024-03-10 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV005396718 | SCV006053486 | uncertain significance | Lynch syndrome 4; Mismatch repair cancer syndrome 4 | 2022-12-15 | criteria provided, single submitter | clinical testing |