NM_000314.8(PTEN):c.40A>G (p.Arg14Gly) is currently classified as a variant of uncertain significance for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (ACMG Classification Rules Specified for PTEN Variant Curation version 3.0.0). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column). PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (PMID:28526761) PS3_P: Other studies demonstrating lipid phosphatase activity <50% of wild-type or abnormal in vitro cellular assay or transgenic model with phenotype different from wild-type that does not meet PS3_moderate. Mingo et al. 2018 (PMID: 29706633). PM2_Supporting: Absent in large sequenced populations OR present at extremely low (<0.00001, 0.001%) allele frequency in the gnomAD cohort. (PMID 27535533). PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease. PP3: in silico REVEL score of 0.811 (>0.7)