ClinVar Miner

Submissions for variant NM_000402.4(G6PD):c.1466G>T (p.Arg489Leu) (rs72554665)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000756195 SCV000883924 pathogenic not provided 2018-01-29 criteria provided, single submitter clinical testing The G6PD c.1376G>T; p.Arg459Leu variant (rs72554665) has been reported in patients of East Asian descent diagnosed with G6PD deficiency (Stevens 1990, Tang 1992). Patients carrying this variant have been shown to have G6PD enzymatic activity lower than levels found in the general Chinese population (Tang 1992). The variant is reported in ClinVar (Variation ID: 100058), and observed in the general population databases at a frequency of 0.16% in the 1000 Genomes Project (0.8% in the East Asian population), and 0.07% in the Genome Aggregation Database (1.0% in the East Asian population). The arginine at codon 459 is moderately conserved and located in the dehydrogenase domain. Based on the above information, the variant is classified as pathogenic. References: Stevens D et al. G6PD Canton a common deficient variant in South East Asia caused by a 459 Arg----Leu mutation. Nucleic Acids Res. 1990: 18(23):7190. Tang T et al. Diverse point mutations result in glucose-6-phosphate dehydrogenase (G6PD) polymorphism in Taiwan. Blood. 1992: 79(8):2135-40.
Counsyl RCV000174272 SCV000677945 pathogenic Anemia, nonspherocytic hemolytic, due to G6PD deficiency 2015-06-06 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000756195 SCV000225548 pathogenic not provided 2015-11-09 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000375428 SCV000482066 pathogenic Glucose 6 phosphate dehydrogenase deficiency 2019-04-05 criteria provided, single submitter clinical testing The G6PD c.1376G>T (p.Arg459Leu) missense variant, also described as G6PD Canton, is one of the most common glucose-6-phosphate dehydrogenase (G6PD) deficiency variants in certain Asian populations. Across a selection of the available literature, the p.Arg459Leu variant was observed in 116 G6PD deficiency cases, mostly in individuals of Chinese ancestry (Stevens et al. 1990; Tang et al. 1992; Cai et al. 2000; Deng et al. 2007; Phompradit et al. 2011; Yang et al. 2014). Control data are unavailable for the p.Arg459Leu variant, which is reported at a frequency of 0.01061 in the East Asian population of the Genome Aggregation Database including 42 hemizygotes in this population and 43 hemizygotes in the total population. Based on the evidence, the p.Arg459Leu variant is classified as pathogenic for glucose-6-phosphate dehydrogenase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000174272 SCV000768476 pathogenic Anemia, nonspherocytic hemolytic, due to G6PD deficiency 2018-12-17 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 459 of the G6PD protein (p.Arg459Leu). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and leucine. This variant has been reported to segregate with glucose-6-phosphate deficiency in two families (PMID: 1562739, 10643148) and it has been reported in many individuals with this condition, particularly those in Chinese subpopulations as well as in other Asian populations (PMID: 2263506, 6714986, 26823837, 25775246, 25541721, 17726510, 20203002, 11499668, 8537082, 21446359). It is also known as the Canton variant in the literature. ClinVar contains an entry for this variant (Variation ID: 100058). Experimental studies have shown that this missense change causes a significant reduction in enzyme activity and affinity for glucose-6-phosphate (PMID: 16607506). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000011104 SCV000031331 other G6PD CANTON 2017-05-24 no assertion criteria provided literature only
OMIM RCV000011105 SCV000031332 other G6PD GIFU 2017-05-24 no assertion criteria provided literature only
OMIM RCV000011106 SCV000031333 other G6PD AGRIGENTO 2017-05-24 no assertion criteria provided literature only
OMIM RCV000011107 SCV000031334 other G6PD TAIWAN-HAKKA 2017-05-24 no assertion criteria provided literature only

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