Submissions for variant NM_000314.8(PTEN):c.870del (p.Glu291fs)

dbSNP: rs886041332

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000340267	SCV000329759	pathogenic	not provided	2016-05-04	criteria provided, single submitter	clinical testing	The c.870delA pathogenic variant in the PTEN gene has been reported previously in an individual with Cowden syndrome (Tan et al., 2011). The deletion causes a frameshift starting with codon Glutamic acid 291, changes this amino acid to a Lysine residue and creates a premature Stop codon at position 16 of the new reading frame, denoted p.Glu291LysfsX16. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, we interpret c.870delA as a pathogenic variant.
Ambry Genetics	RCV000490889	SCV000580001	pathogenic	Hereditary cancer-predisposing syndrome	2018-06-16	criteria provided, single submitter	clinical testing	The c.870delA pathogenic mutation, located in coding exon 8 of the PTEN gene, results from a deletion of one nucleotide at nucleotide position 870, causing a translational frameshift with a predicted alternate stop codon (p.E291Kfs*16). This alteration has been detected in a cohort of patients who met clinical diagnostic criteria for Cowden syndrome (CS) or relaxed clinical diagnostic criteria for CS (Heald B et al. Gastroenterology, 2010 Dec;139:1927-33; Tan MH et al. Am. J. Hum. Genet., 2011 Jan;88:42-56; Ngeow J et al. J. Clin. Endocrinol. Metab., 2011 Dec;96:E2063-71; Nizialek EA et al. Eur. J. Hum. Genet., 2015 Nov;23:1538-43). 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.