ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.541T>C (p.Tyr181His)

dbSNP: rs863224680
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000199773 SCV000254614 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-12-14 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 181 of the PMS2 protein (p.Tyr181His). 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: 216459). 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 with a positive predictive value of 80%. 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 RCV001024078 SCV001186036 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-23 criteria provided, single submitter clinical testing The p.Y181H variant (also known as c.541T>C), located in coding exon 6 of the PMS2 gene, results from a T to C substitution at nucleotide position 541. The tyrosine at codon 181 is replaced by histidine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV001024078 SCV001341282 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-24 criteria provided, single submitter clinical testing

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