ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.615G>T (p.Gln205His)

gnomAD frequency: 0.00001  dbSNP: rs752499497
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Total submissions: 8
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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 (formerly Invitae), Labcorp RCV000468010 SCV000552005 likely benign Hereditary nonpolyposis colorectal neoplasms 2025-01-12 criteria provided, single submitter clinical testing
GeneDx 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, LLC DBA Color Health 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, National Institutes of Health 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, Sinai Health System RCV005396718 SCV006053486 uncertain significance Lynch syndrome 4; Mismatch repair cancer syndrome 4 2022-12-15 criteria provided, single submitter clinical testing

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