ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.599T>C (p.Phe200Ser) (rs786204867)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PTEN Variant Curation Expert Panel RCV000802437 SCV001335277 uncertain significance PTEN hamartoma tumor syndrome 2020-03-23 reviewed by expert panel curation PTEN c.599T>C (p.Phe200Ser) 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). PS4_M: Probands with phenotype specificity score of 2-3.5. (internal laboratory contributor SCV000222124.11) 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.
GeneDx RCV000169807 SCV000222124 likely pathogenic not provided 2018-02-02 criteria provided, single submitter clinical testing A variant that is likely pathogenic has been identified in the PTEN gene. The F200S variant has been reported in one individual referred for PTEN clinical testing, however detailed clinical information and segregation analysis was not reported (Pilarski 2011). The F200S variant is not observed in large population cohorts (Lek et al., 2016). The F200S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Missense variants in nearby residues reported in the Human Gene Mutation Database in individuals with PTEN-related disorders (Stenson et al., 2014). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Invitae RCV000802437 SCV000942269 uncertain significance PTEN hamartoma tumor syndrome 2019-08-22 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with serine at codon 200 of the PTEN protein (p.Phe200Ser). The phenylalanine residue is highly conserved and there is a moderate physicochemical difference between phenylalanine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with suspected PTEN hamartoma tumor syndrome (PMID: 21659347). ClinVar contains an entry for this variant (Variation ID: 189414). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Mendelics RCV000802437 SCV001138135 likely pathogenic PTEN hamartoma tumor syndrome 2019-05-28 criteria provided, single submitter clinical testing

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