ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.416A>G (p.His139Arg)

dbSNP: rs876658142
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000216592 SCV000272986 uncertain significance Hereditary cancer-predisposing syndrome 2020-10-13 criteria provided, single submitter clinical testing The p.H139R variant (also known as c.416A>G), located in coding exon 5 of the PMS2 gene, results from an A to G substitution at nucleotide position 416. The histidine at codon 139 is replaced by arginine, an amino acid with highly similar properties. Based on protein sequence alignment, this amino acid position is highly 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.
Invitae RCV002518233 SCV003348596 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-07-19 criteria provided, single submitter clinical testing 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PMS2 protein function. ClinVar contains an entry for this variant (Variation ID: 229687). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 139 of the PMS2 protein (p.His139Arg).

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