Submissions for variant NM_001360016.2(G6PD):c.1104G>C (p.Glu368Asp)

dbSNP: rs1421656710

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001915236	SCV002176405	uncertain significance	Anemia, nonspherocytic hemolytic, due to G6PD deficiency	2021-08-26	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid with aspartic acid at codon 368 of the G6PD protein (p.Glu368Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with G6PD-related conditions. 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 expected to disrupt G6PD 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.
Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center	RCV004784004	SCV005397784	uncertain significance	Malaria, susceptibility to	2024-06-07	criteria provided, single submitter	clinical testing	This sequence variant is a single nucleotide substitution (G>C) at position 1104 of the coding sequence of the G6PD gene that results in a glutamic acid to aspartic acid amino acid change at residue 368 of the glucose-6-phosphate dehydrogenase protein. This is a previously reported variant (ClinVar 1398795) that has not been observed in individuals affected by a G6PD-related disorder in the published literature, to our knowledge. This variant is absent from the gnomAD v4.1.0 population database (0/~1209000 alleles). Multiple bioinformatic tools predict that this amino acid change would be damaging, and the Glu368 residue at this position is highly conserved across the vertebrate species examined. Studies examining the functional consequence of this variant have not been published, to our knowledge. At this time, there is insufficient evidence to determine if this variant is pathogenic or benign. Therefore, we consider this a variant of uncertain significance. ACMG Criteria: PM2, PP3