ClinVar

Description

Variant summary: SLC2A1 c.2T>G (p.Met1Arg) alters the initiation codon and is predicted to result either in absence of the protein or truncation of the encoded protein due to translation initiation at a downstream codon. Two of three in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 130720 control chromosomes. To our knowledge, no occurrence of c.2T>G in individuals affected with GLUT1 Deficiency Syndrome 1 and no experimental evidence demonstrating its impact on protein function have been reported. However, other initiation codon variants have been reported in association with Glucose transporter type 1 deficiency syndrome as de novo mutations (c.3G>A, c.2T>C, c.1A>G; PMID: 20129935, 26193382). Additionally, GLUT1DS often presents as a haploinsufficiency disorder resulting from de novo SLC2A1 mutations in most cases, or an autosomal dominant pattern of inheritance (PMID: 11603379, etc). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.