ClinVar

Description

The c.170delT pathogenic mutation, located in coding exon 3 of the PTEN gene, results from a deletion of one nucleotide at nucleotide position 170, causing a translational frameshift with a predicted alternate stop codon. One study identified this mutation in 1 of 146 individuals with a deleterious germline PTEN mutation recruited from the Institut Bergonié genetic laboratory to better define cancer risks in PTEN-hamartoma tumor syndrome (PHTS). The authors reported this individual to be affected with colon and ovarian cancer, oral mucosal papillomas, acral keratoses; macrocephaly, gastrointestinal polyps, thyroid cancer and benign thyroid lesions (Bubien V et al. J Med Genet. 2013;50(4):255-63). Different deletions, c.179delA and c.180delG, resulting in a stop codon at the same position (amino acid 98), have also been reported in individuals affected with PHTS (Delatycki et al. J Med Genet. 2003; 40(8); Marchese et al. Am. J. Med. Genet. 2003; 120A(2): 286-8). In addition to the clinical data presented in the literature, since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).