ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.755A>G (p.Asp252Gly) (rs121909239)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PTEN Variant Curation Expert Panel RCV000758222 SCV000886855 likely pathogenic PTEN hamartoma tumor syndrome 2018-07-25 reviewed by expert panel curation PTEN c.755A>G (p.D252G) meets criteria to be classified as likely pathogenic 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). PM6: Assumed de novo, but without confirmation of paternity and maternity in a patient with the disease and no family history. (PMID 23335809, personal communication with corresponding author) PS4_M: Probands with phenotype specificity score of 2-3.5. (PMID 23335809, 15805158) 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. PS3_P: Abnormal in vitro cellular assay or transgenic model with phenotype different from wild type that does not meet PS3. (PMID 21828076, 29706633, 25527629, 29706350)
Invitae RCV000758222 SCV000946953 likely pathogenic PTEN hamartoma tumor syndrome 2019-12-03 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 252 of the PTEN protein (p.Asp252Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with PTEN hamartoma tumor syndrome (PMID: 23335809). ClinVar contains an entry for this variant (Variation ID: 7849). This variant has been reported to affect PTEN protein function (PMID: 25527629, 26579216, 29373119). 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.
OMIM RCV000008299 SCV000028506 pathogenic Macrocephaly/autism syndrome 2005-04-01 no assertion criteria provided literature only

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