ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.364A>G (p.Ile122Val) (rs786202740)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PTEN Variant Curation Expert Panel RCV000541717 SCV000930142 uncertain significance PTEN hamartoma tumor syndrome 2018-07-25 reviewed by expert panel curation PTEN c.364A>G (p.Ile122Val) is currently classified as a variant of uncertain significance for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (PMID 30311380). Please see a summary of the rules and criteria codes in the "PTEN ACMG Specifications Summary" document (assertion method column). PM2: Absent in large sequenced populations (PMID 27535533). PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease. BS3: Missense variants with both lipid phosphatase activity AND results from a second assay appropriate to the protein domain demonstrating no statistically significant difference from wild type. (PMID 21828076, 29706350, 29785012)
Ambry Genetics RCV000165704 SCV000216445 uncertain significance Hereditary cancer-predisposing syndrome 2014-08-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,In silico models in agreement (benign),Other data supporting benign classification
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000178759 SCV000230910 uncertain significance not provided 2015-04-16 criteria provided, single submitter clinical testing
Invitae RCV000541717 SCV000645573 uncertain significance PTEN hamartoma tumor syndrome 2017-04-20 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 122 of the PTEN protein (p.Ile122Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in the germline of individuals with a PTEN-related disease. ClinVar contains an entry for this variant (Variation ID: 186161). Experimental studies have shown that this missense change does not affect PTEN PIP3 phosphatase activity (PMID: 21828076). In summary, this variant is a rare missense change that has been shown not to effect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000165704 SCV000691163 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-31 criteria provided, single submitter clinical testing

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