ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.350A>G (p.Asn117Ser) (rs551221430)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000196078 SCV000254526 uncertain significance PTEN hamartoma tumor syndrome 2018-12-24 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 117 of the PTEN protein (p.Asn117Ser). The asparagine residue is moderately 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 been reported in an individual affected with Parkinson’s disease (PMID: 26362251). ClinVar contains an entry for this variant (Variation ID: 216421). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
GeneDx RCV000483717 SCV000572026 uncertain significance not provided 2018-07-23 criteria provided, single submitter clinical testing This variant is denoted PTEN c.350A>G at the cDNA level, p.Asn117Ser (N117S) 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 a pathogenic or benign germline variant; however, it has been reported as a somatic variant in a lung tumor (Kim 2014). PTEN Asn117Ser was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the phosphatase domain (Molinari 2014). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether PTEN Asn117Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000572974 SCV000663571 uncertain significance Hereditary cancer-predisposing syndrome 2017-04-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence

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