ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.384G>C (p.Lys128Asn) (rs1114167645)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000490879 SCV000580004 likely pathogenic Hereditary cancer-predisposing syndrome 2016-06-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Other data supporting pathogenic classification
Invitae RCV000538530 SCV000645576 likely pathogenic PTEN hamartoma tumor syndrome 2017-08-14 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 128 of the PTEN protein (p.Lys128Asn). The lysine residue is highly 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 been reported as de novo in an individual with symptoms consistent with Bannayan-Riley-Ruvalcaba syndrome (PMID: 17526800). It has also been reported in individuals affected with Cowden syndrome or Cowden syndrome-like symptoms (PMID: 25669429, 23399955). ClinVar contains an entry for this variant (Variation ID: 428220). An experimental study in yeast cells has shown that this missense change, as well as other amino acid substitutions at this residue (p.Lys128Ala, p.Lys128Arg, p.Lys128Thr), disrupts the PIP3 phosphatase activity of the PTEN protein (PMID: 21828076). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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