Submissions for variant NM_005670.4(EPM2A):c.148G>A (p.Gly50Arg)

gnomAD frequency: 0.00029  dbSNP: rs753397854

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000426321	SCV000240971	uncertain significance	not provided	2024-10-10	criteria provided, single submitter	clinical testing	Reported homozygous in a patient with learning difficulties and epilepsy in published literature; however, it is unclear if this individual harbored other variants that could contribute to their phenotype (PMID: 36703223); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27036853, 36703223)
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000426321	SCV000511022	uncertain significance	not provided	2017-01-26	criteria provided, single submitter	clinical testing	Converted during submission to Uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000638309	SCV000759803	uncertain significance	Progressive myoclonic epilepsy	2022-10-17	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 50 of the EPM2A protein (p.Gly50Arg). This variant is present in population databases (rs753397854, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with EPM2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 205424). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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	RCV002317094	SCV000851354	uncertain significance	Inborn genetic diseases	2018-03-19	criteria provided, single submitter	clinical testing	The p.G50R variant (also known as c.148G>A), located in coding exon 1 of the EPM2A gene, results from a G to A substitution at nucleotide position 148. The glycine at codon 50 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Mayo Clinic Laboratories, Mayo Clinic	RCV000426321	SCV001714197	uncertain significance	not provided	2019-04-07	criteria provided, single submitter	clinical testing
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	RCV000426321	SCV002774956	uncertain significance	not provided	2022-12-17	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV003607255	SCV004563357	uncertain significance	Lafora disease	2023-10-06	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000426321	SCV005189276	uncertain significance	not provided		criteria provided, single submitter	not provided