ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.1206A>C (p.Lys402Asn) (rs1064796017)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480141 SCV000572380 uncertain significance not provided 2018-01-16 criteria provided, single submitter clinical testing This variant is denoted PTEN c.1206A>C at the cDNA level, p.Lys402Asn (K402N) at the protein level, and results in the change of a Lysine to an Asparagine (AAA>AAC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PTEN Lys402Asn was not observed in large population cohorts (Lek 2016). This variant is located in PDZ domain binding motif within the C2 domain (Wang 2008). 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 Lys402Asn is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000701845 SCV000830665 uncertain significance PTEN hamartoma tumor syndrome 2018-04-18 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 402 of the PTEN protein (p.Lys402Asn). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PTEN-related disease. ClinVar contains an entry for this variant (Variation ID: 422815). 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.

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