ClinVar

Description

The p.G36E pathogenic mutation (also known as c.107G>A), located in coding exon 2 of the PTEN gene, results from a G to A substitution at nucleotide position 107. The glycine at codon 36 is replaced by glutamic acid, an amino acid with similar properties. This variant was confirmed de novo in a child with clinical features of PTEN hamartoma tumor syndrome (PHTS) (Ambry internal data). Based on an internal structural analysis, this variant is anticipated to result in a significant decrease in structural stability (Lee CU et al. Angew. Chem. Int. Ed. Engl., 2015 Nov;54:13796-800). Another alteration at the same position, p.G36R, has been reported as likely pathogenic based on identification in a proband meeting clinical diagnostic criteria for PHTS and demonstrating deficient phosphatase activity in a functional study (Celebi JT et al. Exp. Dermatol., 2000 Apr;9:152-6; Rodríguez-Escudero I et al. Hum. Mol. Genet., 2011 Nov;20:4132-42). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD) (Lek M et al. Nature, 2016 08;536:285-91). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.