Submissions for variant NM_006516.4(SLC2A1):c.505_507del (p.Leu169del)

dbSNP: rs80359832

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000478031	SCV000566520	pathogenic	not provided	2017-01-10	criteria provided, single submitter	clinical testing	The c.505_507delCTC pathogenic variant in the SLC2A1 gene has been reported multiple times previously (as 686delCTC or 684-686delCTC due to alternative nomenclature) in association with glucose transporter type 1 deficiency syndrome (Glut1-DS) (Pascual et al., 2002; Wang et al., 2005;). The c.505_507delCTC variant causes an in-frame deletion of a Leucine residue at codon 169, denoted p.Leu169del. The c.505_507delCTC variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).
Labcorp Genetics (formerly Invitae), Labcorp	RCV001851153	SCV002245722	pathogenic	GLUT1 deficiency syndrome 1, autosomal recessive	2024-02-24	criteria provided, single submitter	clinical testing	This variant, c.505_507del, results in the deletion of 1 amino acid(s) of the SLC2A1 protein (p.Leu169del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with autosomal dominant glucose transporter deficiency syndrome (PMID: 15622525, 20129935, 31302675). In at least one individual the variant was observed to be de novo. This variant is also known as 684-686delCTC. ClinVar contains an entry for this variant (Variation ID: 419011). For these reasons, this variant has been classified as Pathogenic.
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002470868	SCV002767188	pathogenic	Childhood onset GLUT1 deficiency syndrome 2	2022-02-02	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with dystonia 9 (MIM#601042), infantile-onset GLUT1 deficiency syndrome 1 (MIM#606777), childhood-onset GLUT1 deficiency syndrome 2 (GDS) (MIM#612126) and stomatin-deficient cryohydrocytosis with neurologic defects, (MIM#608885). (I) 0107 - This gene is associated with autosomal dominant disease. Autosomal recessive disease has been rarely reported (OMIM). (I) 0112 - The condition associated with this gene has incomplete penetrance. Individuals with missense variants causing GDS or epilepsy have been reported with incomplete penetrance, but this is a rare occurrence (OMIM, PMID: 18451999). (I) 0115 - Variants in this gene are known to have variable expressivity within families with GDS (PMID: 20129935). (I) 0213 - In-frame deletion in a non-repetitive region that has high conservation. (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported as pathogenic, and observed in multiple individuals with early onset refractory seizures and/or GLUT1 deficiency syndrome. The variant in two of these individuals was confirmed de novo (ClinVar, PMID: 30271476, PMID: 20129935, PMID: 26193382). (SP) 1102 - Strong phenotype match for this individual. (SP) 1204 - This variant has been shown to be de novo in the proband (parental status not tested but assumed). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Genome-Nilou Lab	RCV003446077	SCV004173433	pathogenic	Encephalopathy due to GLUT1 deficiency	2023-04-11	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV003446077	SCV004242470	likely pathogenic	Encephalopathy due to GLUT1 deficiency	2023-12-18	criteria provided, single submitter	clinical testing	Criteria applied: PS4_MOD,PM4,PM6,PM2_SUP