ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.722T>C (p.Phe241Ser) (rs121909240)

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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 RCV000645053 SCV000886867 likely pathogenic PTEN hamartoma tumor syndrome 2018-11-28 reviewed by expert panel curation PTEN c.722T>C (p.Phe241Ser) 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). PS3: Phosphatase activity <50% of wild type (PMID 29706350, 29785012, 26579216, 25527629, 21828076) 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. PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (PMID 15805158)
Invitae RCV000645053 SCV000766793 uncertain significance PTEN hamartoma tumor syndrome 2017-12-11 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with serine at codon 241 of the PTEN protein (p.Phe241Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with autism and macrocephaly (PMID: 15805158). ClinVar contains an entry for this variant (Variation ID: 7850). Experimental studies have shown that this missense change creates an unstable protein and partially affects the phosphatase activity of the PTEN protein (PMID: 21828076, 25527629).  An additional study showed that this variant fails to suppress tyrosine hydroxylase activity in mouse PC12 cells (PMID: 26579216). 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.
OMIM RCV000008300 SCV000028507 pathogenic Macrocephaly/autism syndrome 2005-04-01 no assertion criteria provided literature only

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