ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.518G>C (p.Arg173Pro) (rs121913294)

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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 RCV000164565 SCV000215223 likely pathogenic Hereditary cancer-predisposing syndrome 2014-06-17 criteria provided, single submitter clinical testing Well-characterized mutation at same position;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;Other strong data supporting pathogenic classification
Invitae RCV000645030 SCV000766769 likely pathogenic PTEN hamartoma tumor syndrome 2019-11-14 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 173 of the PTEN protein (p.Arg173Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with adult-onset Lhermitte-Duclos disease (PMID: 19719509), and an individual with Cowden syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 185195). Experimental studies have shown that this missense change abolishes PTEN phosphatase activity in vitro (PMID: 10866302). A different missense substitution at this codon (p.Arg173Cys) has been determined to be pathogenic (PMID: 17526800, 25669429, 24778394, 22628360, 10866302). This suggests that the arginine residue is critical for PTEN protein function and that other missense substitutions at this position may also be pathogenic. 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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