ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.349A>C (p.Asn117His) (rs771310592)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165033 SCV000215730 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other strong data supporting pathogenic classification,Insufficient or conflicting evidence
GeneDx RCV000216601 SCV000279916 uncertain significance not provided 2016-10-11 criteria provided, single submitter clinical testing This variant is denoted PTEN c.349A>C at the cDNA level, p.Asn117His (N117H) at the protein level, and results in the change of an Asparagine to a Histidine (AAT>CAT). This variant was observed in a cohort of individuals undergoing hereditary cancer panel testing for a personal and/or family history suspicious for Lynch syndrome (Yurgelun 2015). PTEN Asn117His was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Asparagine and Histidine differ in some properties, this is considered a semi-conservative amino acid substitution. PTEN Asn117His occurs at a position that is conserved across species and is located in the phosphatase domain (Molinari 2014). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether PTEN Asn117His is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000524733 SCV000645572 uncertain significance PTEN hamartoma tumor syndrome 2017-10-17 criteria provided, single submitter clinical testing This sequence change replaces asparagine with histidine at codon 117 of the PTEN protein (p.Asn117His). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and histidine. The frequency data for this variant (rs771310592) in the population databases is unreliable, as metrics indicate poor quality at this position in the ExAC database. This variant has been reported in the literature in an individual undergoing genetic testing for suspected Lynch syndrome (PMID: 25980754). ClinVar contains an entry for this variant (Variation ID: 185588). 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. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance
Color RCV000165033 SCV000912946 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-25 criteria provided, single submitter clinical testing

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