ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.941A>C (p.Glu314Ala) (rs1171478249)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520987 SCV000620797 uncertain significance not provided 2017-09-22 criteria provided, single submitter clinical testing The E314A variant in the PTEN gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The E314A variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The E314A variant is a non-conservative amino acid substitution, which occurs within the C2 domain where amino acids with similar properties to Glutamic acid are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret E314A as a variant of uncertain significance.
Invitae RCV000525707 SCV000645635 uncertain significance PTEN hamartoma tumor syndrome 2017-11-17 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with alanine at codon 314 of the PTEN protein (p.Glu314Ala). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid and alanine. 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. 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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