ClinVar

Description

Variant summary: PTEN c.755A>T (p.Asp252Val) results in a non-conservative amino acid change in the encoded protein sequence. A different variant at the same codon, c.755A>G (p.Asp252Gly) has been classified as Likely pathogenic/pathogenic supporting the critical relevance of the Aspartate 252 residue to PTEN protein function. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251422 control chromosomes. c.755A>T has been reported in the literature in individuals affected with autism spectrum disorders, PTEN-hamartoma syndrome, Cowden syndrome and in settings of Thyroid nodules (example, Frazier_2015, Kim_2022, Yehia_2022, Nizialek_2015, Quaytman_2022). These data indicate that the variant may be associated with disease. Several studies have reported an impact on PTEN-function, however, these were not weighted in the context of this evaluation. The following publications have been ascertained in the context of this evaluation (PMID: 25288137, 34492006, 36175890, 29785012, 29706350, 25669429, 31232187, 35723418, 31427284, 25527629, 35241692). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.