Submissions for variant NM_006516.4(SLC2A1):c.287T>C (p.Met96Thr)

dbSNP: rs1643481875

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001051269	SCV001215414	pathogenic	GLUT1 deficiency syndrome 1, autosomal recessive	2023-03-23	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Met96 amino acid residue in SLC2A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20129935, 26598494, 30588498). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SLC2A1 protein function. ClinVar contains an entry for this variant (Variation ID: 847673). This missense change has been observed in individual(s) with clinical features of SLC2A1-related conditions (PMID: 34305802). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 96 of the SLC2A1 protein (p.Met96Thr).
Experimental Epileptology, AG Lerche, Hertie Institute for Clinical Brain Research	RCV001449666	SCV001623015	likely pathogenic	Childhood onset GLUT1 deficiency syndrome 2	2021-05-19	criteria provided, single submitter	research	ACMG Criteria: PM2, PM5, PP1, PP3
Genome-Nilou Lab	RCV003446600	SCV004173539	likely pathogenic	Encephalopathy due to GLUT1 deficiency	2023-04-11	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV003446600	SCV004801416	likely pathogenic	Encephalopathy due to GLUT1 deficiency	2024-03-19	criteria provided, single submitter	clinical testing