Submissions for variant NM_000314.8(PTEN):c.21_22del (p.Glu7fs)

dbSNP: rs786204881

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000169822	SCV000222142	pathogenic	not provided	2017-06-19	criteria provided, single submitter	clinical testing	This deletion causes a frameshift starting with codon Glutamic acid 7, changes this amino acid to an Aspartic acid residue, and creates a premature Stop codon at position 3 of the new reading frame, denoted p.Glu7AspfsX3. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001381867	SCV001580432	pathogenic	PTEN hamartoma tumor syndrome	2023-09-07	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: 189429). This variant is also known as c.18_19delAG. This premature translational stop signal has been observed in individual(s) with clinical features of PTEN hamartoma tumor syndrome (PHTS) (PMID: 21194675, 21659347, 23470840, 27477328). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu7Aspfs*3) 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).
Ambry Genetics	RCV002415718	SCV002728349	pathogenic	Hereditary cancer-predisposing syndrome	2021-09-02	criteria provided, single submitter	clinical testing	The c.21_22delGA pathogenic mutation, located in coding exon 1 of the PTEN gene, results from a deletion of two nucleotides at nucleotide positions 21 to 22, causing a translational frameshift with a predicted alternate stop codon (p.E7Dfs*3). This mutation has been reported in multiple individuals with PTEN hamartoma tumor syndrome (Chen HH et al. J Allergy Clin Immunol 2017 02;139(2):607-620.e15; Tan MH et al. Am J Hum Genet 2011 Jan;88(1):42-56; Busch RM et al. Genet Med 2013 Jul;15(7):548-53; Pilarski R et al. J Med Genet 2011 Aug;48(8):505-12). Of note, this alteration is also designated as c.18_19delAG in published 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.
Myriad Genetics, Inc.	RCV003454435	SCV004189775	pathogenic	Cowden syndrome 1	2023-09-25	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.