ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.830C>G (p.Thr277Arg) (rs398123329)

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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 RCV000536465 SCV001335276 likely pathogenic PTEN hamartoma tumor syndrome 2020-03-23 reviewed by expert panel curation PTEN c.830C>G (p.Thr277Arg) 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) PM2: Absent in large sequenced populations PP1_M: Co-segregation with disease in multiple affected family members, with 5 or 6 meioses observed. (PMID 23335809) 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.
Ambry Genetics RCV000491643 SCV000580063 likely pathogenic Hereditary cancer-predisposing syndrome 2016-04-15 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Structural Evidence;Rarity in general population databases (dbsnp, esp, 1000 genomes);Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Invitae RCV000536465 SCV000645627 pathogenic PTEN hamartoma tumor syndrome 2019-01-08 criteria provided, single submitter clinical testing This sequence change replaces threonine with arginine at codon 277 of the PTEN protein (p.Thr277Arg). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with PTEN-related conditions (PMID: 20712882, 23335809). ClinVar contains an entry for this variant (Variation ID: 428268). This variant has been reported to affect PTEN protein function (PMID: 29706350). For these reasons, this variant has been classified as Pathogenic.

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