ClinVar Miner

Submissions for variant NM_000314.8(PTEN):c.420dup (p.His141fs)

dbSNP: rs1085308050
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Herman Laboratory, Nationwide Children's Hospital RCV000490587 SCV000579276 pathogenic PTEN hamartoma tumor syndrome 2017-03-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV001022058 SCV001183749 pathogenic Hereditary cancer-predisposing syndrome 2019-07-19 criteria provided, single submitter clinical testing The c.420dupA pathogenic mutation, located in coding exon 5 of the PTEN gene, results from a duplication of A at nucleotide position 420, causing a translational frameshift with a predicted alternate stop codon (p.H141Tfs*39). This mutation has been detected in multiple individuals with a clinical diagnosis of Cowden Syndrome (Hansen-Kiss et. al. J. Med. Genet. 2017 07;54(7):471-478; Pilarski et. al. J. Med. Genet. 2011 Aug;48(8):505-12; Holbert et. al. Eur. J. Hum. Genet. 2014 Feb;22(2):273-6). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp RCV000490587 SCV003439627 pathogenic PTEN hamartoma tumor syndrome 2022-05-18 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 427592). This premature translational stop signal has been observed in individual(s) with PTEN-related conditions (PMID: 21659347, 23695273). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.His141Thrfs*39) in the PTEN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PTEN are known to be pathogenic (PMID: 9467011, 21194675).

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