Submissions for variant NM_006516.4(SLC2A1):c.945C>G (p.Ile315Met)

dbSNP: rs780528770

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000189365	SCV000243003	uncertain significance	not provided	2023-03-07	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27149842)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001064748	SCV001229666	uncertain significance	GLUT1 deficiency syndrome 1, autosomal recessive	2024-08-20	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 315 of the SLC2A1 protein (p.Ile315Met). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SLC2A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 207200). Invitae Evidence Modeling incorporating data from in vitro experimental studies (Invitae) indicates that this missense variant is not expected to disrupt SLC2A1 function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV002444767	SCV002683203	uncertain significance	Inborn genetic diseases	2017-12-20	criteria provided, single submitter	clinical testing	The p.I315M variant (also known as c.945C>G), located in coding exon 7 of the SLC2A1 gene, results from a C to G substitution at nucleotide position 945. The isoleucine at codon 315 is replaced by methionine, an amino acid with highly similar properties. This variant did not co-segregate with disease in one individual tested in our laboratory. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003401033	SCV004121899	uncertain significance	not specified	2023-10-19	criteria provided, single submitter	clinical testing	Variant summary: SLC2A1 c.945C>G (p.Ile315Met) results in a conservative amino acid change located in the Major facilitator superfamily domain (IPR020846) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251196 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.945C>G in individuals affected with GLUT1 Deficiency Syndrome 1 and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Genome-Nilou Lab	RCV003445649	SCV004172859	uncertain significance	Epilepsy, idiopathic generalized, susceptibility to, 12	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003445648	SCV004172860	uncertain significance	Dystonia 9	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003445646	SCV004172861	uncertain significance	Encephalopathy due to GLUT1 deficiency	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003445647	SCV004172862	uncertain significance	Childhood onset GLUT1 deficiency syndrome 2	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003445650	SCV004172863	uncertain significance	Hereditary cryohydrocytosis with reduced stomatin	2023-04-11	criteria provided, single submitter	clinical testing