ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1708A>C (p.Asn570His)

dbSNP: rs115670442
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000823449 SCV000964309 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-08-06 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) performed at Invitae indicates that this missense variant is not expected to disrupt PMS2 protein function. ClinVar contains an entry for this variant (Variation ID: 665215). 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 asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 570 of the PMS2 protein (p.Asn570His).
Ambry Genetics RCV001012759 SCV001173253 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-03 criteria provided, single submitter clinical testing The p.N570H variant (also known as c.1708A>C), located in coding exon 11 of the PMS2 gene, results from an A to C substitution at nucleotide position 1708. The asparagine at codon 570 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.
All of Us Research Program, National Institutes of Health RCV004002854 SCV004815859 uncertain significance Lynch syndrome 2023-04-03 criteria provided, single submitter clinical testing This missense variant replaces asparagine with histidine at codon 570 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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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