The NM_004958.4:c.4468T>C variant in MTOR is a missense variant predicted to cause substitution of tryptophan by arginine at amino acid 1490 (p.Trp1490Arg). 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 Expert Panel 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 kinase domain of MTOR that is defined as a critical functional domain by the ClinGen BM VCEP (PMIDs: 23322780, 27482884, 21210909) (PM1_Supporting). This variant has been identified as a de novo occurrence with parental relationships confirmed in one individual with macrocephaly ( >=2 SD) and developmental delay or intellectual disability without cortical malformations (PS2_M, PS4_M; PMID: 27830187). In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal dominant overgrowth with or without cerebral malformations due to abnormalities in MTOR-pathway genes based on the ACMG/AMP criteria applied, as specified by the ClinGen Brain Malformations Expert Panel: PM2_supporting, PP2, PM1_supporting, PS4_moderate, PS2_moderate; 7 points (VCEP specifications version 1.1).