ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.428T>C (p.Ile143Thr)

dbSNP: rs1562690040
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneKor MSA RCV000708733 SCV000822133 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000708733 SCV002630989 uncertain significance Hereditary cancer-predisposing syndrome 2020-01-30 criteria provided, single submitter clinical testing The p.I143T variant (also known as c.428T>C), located in coding exon 5 of the PMS2 gene, results from a T to C substitution at nucleotide position 428. The isoleucine at codon 143 is replaced by threonine, an amino acid with similar properties. This alteration was reported as a variant of unknown significance in 1/1197 individuals from Greece, Romania, and Turkey undergoing evaluation for inherited cancer predisposition (Tsaousis GN et al. BMC Cancer, 2019 Jun;19:535). This amino acid position is not well 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.
Color Diagnostics, LLC DBA Color Health RCV000708733 SCV004359682 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-11 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with threonine at codon 143 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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