ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.467C>T (p.Thr156Ile)

dbSNP: rs1554303953
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000629946 SCV000750902 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-10-19 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 156 of the PMS2 protein (p.Thr156Ile). 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: 525718). 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. 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 RCV001022884 SCV001184671 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-04 criteria provided, single submitter clinical testing The p.T156I variant (also known as c.467C>T), located in coding exon 5 of the PMS2 gene, results from a C to T substitution at nucleotide position 467. The threonine at codon 156 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV004002784 SCV004825016 uncertain significance Lynch syndrome 2023-08-08 criteria provided, single submitter clinical testing This missense variant replaces threonine with isoleucine at codon 156 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.

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