The NM_000156.6: c.677C>T variant in GAMT is a missense variant predicted to result in the substitution of proline for leucine at amino acid 226 (p.Pro226Leu). It is absent in gnomAD v2.1.1 (PM2_Supporting). The computational predictor REVEL gives a score of 0.292 which is below the threshold of 0.5, evidence that does not predict a damaging effect on GAMT function (BP4). To our knowledge, this variant has not been reported in published literature in individuals with GAMT deficiency, and the results of functional studies are unavailable. This variant has been previously reported in ClinVar (Variation ID: 205594). In summary, this variant meets the criteria to be classified as a variant of uncertain significancefor GAMT deficiency. GAMT-specific ACMG/AMP codes met, as specified by the ClinGen Cerebral Creatine Deficiency Syndromes VCEP (Specifications Version 1.1.0): PM2_Supporting, BP4. (Classification approved by the ClinGen CCDS VCEP on June 6, 2022).