ClinVar Miner

Submissions for variant NM_000402.4(G6PD):c.1268G>A (p.Arg423His) (rs137852316)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000756196 SCV000883925 pathogenic not provided 2018-02-13 criteria provided, single submitter clinical testing The G6PD c.1178G>A; p.Arg393His variant (rs137852316), also known as G6PD Nashville and G6PD Anaheim, has been reported in the literature in individuals and families with glucose-6-phosphate dehydrogenase (G6PD) deficiency (Beutler 1991, Filosa 1992). This variant is reported as pathogenic in ClinVar (Variation ID: 10370) and is absent from the general population databases (1000 Genomes Project, Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. Additionally, another variant at this codon (c.1177C>G; p.Arg393Gly) have been reported in individuals with G6PD deficiency and is considered pathogenic (Beutler 1995). The arginine at codon 393 is highly conserved and computation algorithms (SIFT, PolyPhen2, MutationTaster) predict this variant to be deleterious. Further, functional analyses demonstrate protein instability and impairment (Gomez-Manzo 2014, Wang 2006, Wang 2009). Based on the above information, this variant is considered pathogenic. References: Beutler E et al. DNA sequence abnormalities of human glucose-6-phosphate dehydrogenase variants. J Biol Chem. 1991 Mar 5;266(7):4145-50. Beutler E et al. Three new exon 10 glucose-6-phosphate dehydrogenase mutations. Blood Cells Mol Dis. 1995;21(1):64-72. Filosa S et al. Molecular basis of chronic non-spherocytic haemolytic anaemia: a new G6PD variant (393 Arg----His) with abnormal KmG6P and marked in vivo instability. Br J Haematol. 1992 Jan;80(1):111-6. Gomez-Manzo S et al. The Stability of G6PD Is Affected by Mutations with Different Clinical Phenotypes. Int J Mol Sci. 2014 Nov; 15(11): 21179–21201. Wang X et al. Functional properties of two mutants of human glucose 6-phosphate dehydrogenase, R393G and R393H, corresponding to the clinical variants G6PD Wisconsin and Nashville. Biochim Biophys Acta. 2006;1762(8):767-774. Wang X et al. Clinical mutants of human glucose 6-phosphate dehydrogenase: Impairment of NADP+ binding affects both folding and stability. Biochim Biophys Acta. 2009;1792(8):804-809.
OMIM RCV000011090 SCV000031317 other G6PD PORTICI 2013-10-24 no assertion criteria provided literature only
OMIM RCV000030890 SCV000031340 other G6PD NASHVILLE 2017-05-24 no assertion criteria provided literature only
OMIM RCV000030891 SCV000031341 other G6PD ANAHEIM 2017-05-24 no assertion criteria provided literature only
OMIM RCV000066231 SCV000105925 pathogenic Anemia, nonspherocytic hemolytic, due to G6PD deficiency 1992-01-01 no assertion criteria provided literature only

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