Submissions for variant NM_001164277.2(SLC37A4):c.857G>A (p.Arg286Gln)

gnomAD frequency: 0.00019  dbSNP: rs548684318

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000819639	SCV000960310	uncertain significance	Glucose-6-phosphate transport defect	2022-10-24	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 286 of the SLC37A4 protein (p.Arg286Gln). This variant is present in population databases (rs548684318, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with SLC37A4-related conditions. ClinVar contains an entry for this variant (Variation ID: 662077). 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 not expected to disrupt SLC37A4 protein function. 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.
CeGaT Center for Human Genetics Tuebingen	RCV001729714	SCV002563088	uncertain significance	not provided	2021-03-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001729714	SCV002568716	uncertain significance	not provided	2022-08-22	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in a patient with early infantile epileptic encephalopathy, but zygosity and segregation information were not provided, and this patient was also reported to have multiple variants in other genes (Rochtus et al., 2019); This variant is associated with the following publications: (PMID: 30709877)
Ambry Genetics	RCV004678846	SCV005168819	uncertain significance	Inborn genetic diseases	2024-03-22	criteria provided, single submitter	clinical testing	The p.R286Q variant (also known as c.857G>A), located in coding exon 5 of the SLC37A4 gene, results from a G to A substitution at nucleotide position 857. The arginine at codon 286 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.
Natera, Inc.	RCV000819639	SCV001457212	uncertain significance	Glucose-6-phosphate transport defect	2020-04-16	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001729714	SCV001978731	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001729714	SCV001980092	uncertain significance	not provided		no assertion criteria provided	clinical testing