Submissions for variant NM_000402.4(G6PD):c.1246A>G (p.Lys416Glu)

dbSNP: rs137852320

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000294855	SCV000331230	pathogenic	not provided	2016-01-04	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000294855	SCV000883927	pathogenic	not provided	2017-12-07	criteria provided, single submitter	clinical testing
Dunham Lab, University of Washington	RCV002305428	SCV002599363	pathogenic	Anemia, nonspherocytic hemolytic, due to G6PD deficiency	2022-08-12	criteria provided, single submitter	curation	Variant found in unrelated hemizygotes with deficiency and CNSHA (PS4_M, PP4). In one family, hemizygote and heterozygous maternal grandmother have history of hemolytic anemia (PP1). Decreased activity in red blood cells (1-13%) (PS3). Within dimer interface (PM1). Not found in gnomAD (PM2). Reported as pathogenic by multiple clinical testing groups (PP5). Post_P 0.999 (odds of pathogenicity 13661, Prior_P 0.1).
Labcorp Genetics (formerly Invitae), Labcorp	RCV002305428	SCV003445869	pathogenic	Anemia, nonspherocytic hemolytic, due to G6PD deficiency	2025-01-21	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 386 of the G6PD protein (p.Lys386Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with glucose-6-phosphate dehydrogenase deficiency (PMID: 2602358; internal data). This variant is also known as G-6-PD Walter Reed. ClinVar contains an entry for this variant (Variation ID: 10375). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt G6PD protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV002305428	SCV003833787	likely pathogenic	Anemia, nonspherocytic hemolytic, due to G6PD deficiency	2024-01-05	criteria provided, single submitter	clinical testing
OMIM	RCV000011096	SCV000031323	other	G6PD IOWA	2017-05-24	no assertion criteria provided	literature only
OMIM	RCV000011097	SCV000031324	other	G6PD IOWA CITY	2017-05-24	no assertion criteria provided	literature only
OMIM	RCV000011098	SCV000031325	other	G6PD SPRINGFIELD	2017-05-24	no assertion criteria provided	literature only
OMIM	RCV000011099	SCV000031326	other	G6PD WALTER REED	2017-05-24	no assertion criteria provided	literature only
PreventionGenetics, part of Exact Sciences	RCV004748512	SCV005362079	pathogenic	G6PD-related disorder	2024-03-13	no assertion criteria provided	clinical testing	The G6PD c.1156A>G variant is predicted to result in the amino acid substitution p.Lys386Glu. This variant has been reported to be pathogenic for glucose-6-phosphate dehydrogenase deficiency likely due to altered lysine acetylation (Hirono et al. 1989. PubMed ID: 2602358; Suo et al. 2013. PubMed ID: 23298314). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic.