The NM_004958.4:c.5005G>T variant in MTOR is a missense variant predicted to cause substitution of alanine by serine at amino acid 1669. This variant is absent from gnomAD v4.1.0 (PM2_Supporting). MTOR, in which the variant was identified, is defined by the ClinGen Brain Malformations Variant Curation Expert Panel (BM VCEP) as a gene that has a low rate of benign missense variation and where pathogenic missense variants are a common mechanism of disease (PP2). This variant resides within the focal adhesion kinase targeting domain of MTOR that is defined as a critical functional domain by the ClinGen BM VCEP (PM1_Supporting; PMIDs: 23322780, 27482884, 21210909). This variant has been identified in one patient with diffuse cortical dysplasia (PS4_Supporting, PMID: 25599672). In this patient, the variant was present at an alternate allele frequency of 44% in the brain but was not detectable in blood (PS2_Moderate). In summary, this variant meets the criteria to be classified as likely pathogenic for overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes based on the ACMG/AMP criteria applied, as specified by the ClinGen BM VCEP Panel: PM2_Supporting, PP2, PM1_Supporting, PS4_Supporting, PS2_Moderate (ClinGen Brain Malformations VCEP Specifications Version 1.1).