ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.212A>G (p.Asn71Ser) (rs587780049)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000759919 SCV000149584 uncertain significance not provided 2014-03-24 criteria provided, single submitter clinical testing This variant is denoted PMS2 c.212A>G at the cDNA level, p.Asn71Ser (N71S) at the protein level, and results in the change of an Asparagine to a Serine (AAT>AGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PMS2 Asn71Ser was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Asparagine and Serine share similar properties, this is considered a conservative amino acid substitution and is unlikely to affect protein integrity. PMS2 Asn71Ser occurs at a position that is well conserved across species and is located in the ATPase domain (Fukui 2011). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether PMS2 Asn71Ser is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000558750 SCV000625582 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-09-10 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 71 of the PMS2 protein (p.Asn71Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 127774). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759919 SCV000889622 uncertain significance not provided 2017-09-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV001014552 SCV001175273 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-03 criteria provided, single submitter clinical testing Insufficient evidence

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