ClinVar Miner

Submissions for variant NM_000314.8(PTEN):c.405dup (p.Cys136fs)

dbSNP: rs398123323
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162814 SCV000213296 pathogenic Hereditary cancer-predisposing syndrome 2020-06-15 criteria provided, single submitter clinical testing The c.405dupA pathogenic mutation, located in coding exon 5 of the PTEN gene, results from a duplication of A at nucleotide position 405, causing a translational frameshift with a predicted alternate stop codon (p.C136Mfs*44). This mutation has been reported in multiple individuals with personal and/or family history consistent with Cowden syndrome (Tan MH et al. Am J Hum Genet. 2011;88(1):42-56; Pilarski R et al. J Med Genet. 2011;48(8):505-12; Patraquim C et al. Case Rep Pediatr, 2017 Jan;2017:2750523; Heald B et al. Gastroenterology, 2010 Dec;139:1927-33). Of note, this alteration is also designated as 406insA and c.405_406insA in the literature. 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.
GeneDx RCV000078617 SCV000490752 pathogenic not provided 2016-12-01 criteria provided, single submitter clinical testing The c.405dupA pathogenic variant in the PTEN gene has been reported previously in association with PTEN hamartoma tumor syndrome (O'Roak et al., 2012). This duplication causes a frameshift starting with codon Cysteine 136, changes this amino acid to a Methionine residue and creates a premature Stop codon at position 44 of the new reading frame, denoted p.Cys136MetfsX44. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.
Myriad Genetics, Inc. RCV003450653 SCV004189736 pathogenic Cowden syndrome 1 2023-09-27 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
OMIM RCV000032874 SCV000056644 pathogenic Macrocephaly-autism syndrome 2012-12-21 no assertion criteria provided literature only

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