Submissions for variant NM_000156.6(GAMT):c.577C>T (p.Gln193Ter)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003230881	SCV003928814	pathogenic	Deficiency of guanidinoacetate methyltransferase	2023-04-12	criteria provided, single submitter	clinical testing	Variant summary: GAMT c.577C>T (p.Gln193X) results in a premature termination codon, located in the last exon, therefore it is not expected to cause nonsense mediated decay (NMD), but is predicted to cause a truncation of the encoded protein, removing a part of the 236 amino acid long protein. Truncations downstream of this position have been reported in affected individuals (HGMD). The variant was absent in 242348 control chromosomes (gnomAD). c.577C>T has been reported in the literature in multiple homozygous individuals affected with Cerebral Creatine Deficiency Syndrome 2 (Cheillan_2012, Monies_2019). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.