ClinVar Miner

Submissions for variant NM_000314.8(PTEN):c.723del (p.Phe241fs)

dbSNP: rs1060500115
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000826203 SCV000967759 pathogenic PTEN hamartoma tumor syndrome 2018-04-27 criteria provided, single submitter clinical testing The p.Phe241fs variant in PTEN has been reported in one individual with PTEN-ham artoma tumor syndrome (PHTS) and eosinophilic gastrointestinal disorders (Hender son 2014), and was absent from large population studies. This variant is predict ed to cause a frameshift, which alters the protein?s amino acid sequence beginni ng at position 241 and leads to a premature termination codon 15 amino acids dow nstream. This alteration is then predicted to lead to a truncated or absent prot ein. Heterozygous loss of function of the PTEN gene is an established disease me chanism in PHTS. Additionally, two other variants at this position have been rep orted in individuals with macrocephaly and PTEN-related tumors (Marsh 1998, Buis son 2006). In summary, this variant meets criteria to be classified as pathogeni c for PHTS in an autosomal dominant manner based upon the predicted impact on th e protein. ACMG/AMP Criteria applied: PVS1, PMS2, PS4_Supporting.
Breda Genetics srl RCV001265533 SCV001443276 pathogenic PTEN-related disorder 2020-07-31 criteria provided, single submitter clinical testing The variant c.723del (p.Phe241Leufs*15) in the PTEN gene is reported as pathogenic for PTEN hamartoma tumor syndrome in ClinVar (Variation ID: 667418). The variant creates a shift in the reading frame which is predicted to result in a premature stop codon 15 amino acids downstream, which is likely to result in a truncated protein or protein loss due to nonsense-mediated messenger decay (NMD). This variant has not been reported in dbSNP, gnomAD, 1000 Genomes, NHLI Exome Sequencing Project (ESP). This pathogenic variant has already been reported by Henderson et al. (2014) in a pediatric case of PTEN hamartoma tumor syndromes (PMID: 24345843). Moreover, the variant falls in a region rich in pathogenic frameshift mutation in Clinvar.
Myriad Genetics, Inc. RCV003453760 SCV004188918 pathogenic Cowden syndrome 1 2023-09-29 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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