ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.2315C>T (p.Thr772Ile)

dbSNP: rs1781849852
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001319491 SCV001510235 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-11-28 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 772 of the PMS2 protein (p.Thr772Ile). The frequency data for this variant in the population databases (gnomAD) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. 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: 1019979). Invitae Evidence Modeling incorporating data from in vitro experimental studies (internal data) indicates that this missense variant is not expected to disrupt PMS2 function with a negative predictive value of 95%. 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.
Baylor Genetics RCV003462891 SCV004205426 uncertain significance Lynch syndrome 4 2023-09-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV004034974 SCV005036013 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-19 criteria provided, single submitter clinical testing The p.T772I variant (also known as c.2315C>T), located in coding exon 14 of the PMS2 gene, results from a C to T substitution at nucleotide position 2315. The threonine at codon 772 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is conserved. 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.

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