ClinVar Miner

Submissions for variant NM_000402.4(G6PD):c.934G>C (p.Asp312His) (rs137852318)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000757322 SCV000885497 pathogenic not provided 2017-08-01 criteria provided, single submitter clinical testing The G6PD c.844G>C; p.Asp282His variant (rs137852318), also known as G6PD Seattle/Ferrara II/Modena/Athens-like, has been reported in multiple individuals in the Mediterranean region with G6PD deficiency (Cappellini 1994, Cappellini 1995, De Vita 1989, Frigerio 1994, Lenzerini 1969, Rattazzi 1969). Functional characterization indicates enzymatic activity ranging from 15 to 25 percent of wildtype (Cappellini 1994, Cappellini 1995, De Vita 1989, Frigerio 1994, Lenzerini 1969, Rattazzi 1969), consistent with a class III variant (WHO working group 1989). The variant is listed as pathogenic in ClinVar (Variation ID: 10372), and observed in the general population databases at a frequency of 0.07% (143/200329 alleles, including 52 hemizygotes) in the Genome Aggregation Database. The aspartate at codon 282 is moderately conserved, and computational algorithms (Mutation Taster, PolyPhen-2, SIFT) predict that the variant has an impact on the protein. Based on the available information, this variant is classified as pathogenic. REFERENCES Cappellini M et al. Biochemical and molecular characterization of a new sporadic glucose-6-phosphate dehydrogenase variant described in Italy: G6PD Modena. Br J Haematol. 1994; 87(1):209-11. Cappellini M et al. Molecular characterisation of the glucose-6-phosphate dehydrogenase (G6PD) Ferrara II variant. Hum Genet. 1995; 95(4):440-2. De Vita G et al. Two point mutations are responsible for G6PD polymorphism in Sardinia. Am J Hum Genet. 1989; 44(2):233-40. Frigerio R et al. Molecular and biochemical data on some glucose-6-phosphate dehydrogenase variants from southern Sardinia. Haematologica. 1994; 79(4):319-21. Lenzerin L et al. Characterization of glucose-6-phosphate dehydrogenase variants. I. Occurrence of a G6PD Seattle-like variant in Sardinia and its interaction with the G6PD Mediterranean variant. Am J Hum Genet. 1969; 21(2):142-53. Rattazzi M et al. Characterization of glucose-6-phosphate dehydrogenase variants. II. G6PD Kephalonia, G6PD Attica, and G6PD Seattle-like" found in Greece. Am J Hum Genet. 1969; 21(2):154-67. WHO working group. Glucose-6-phosphate dehydrogenase deficiency. Bull World Health Organ. 1989; 67(6):601-11. "
Courtagen Diagnostics Laboratory,Courtagen Life Sciences RCV000180200 SCV000236504 pathogenic Anemia, nonspherocytic hemolytic, due to G6PD deficiency 2014-04-10 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000757322 SCV000232594 pathogenic not provided 2013-11-12 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763204 SCV000893823 pathogenic Susceptibility to malaria; Anemia, nonspherocytic hemolytic, due to G6PD deficiency 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000180200 SCV000647803 pathogenic Anemia, nonspherocytic hemolytic, due to G6PD deficiency 2018-11-20 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with histidine at codon 282 of the G6PD protein (p.Asp282His). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and histidine. This variant is present in population databases (rs137852318, ExAC 0.1%). This variant is a well-known G6PD  mutation which has been reported in multiple individuals from different ethnic groups affected with G6PD deficiency and there is evidence of disease co-segregation in families (PMID: 7806085, 2912069, 7947250, 8807321, 7947239, 5305539). This variant is also known as the Seattle-like, the Ferrara 2, the Athens-like, or the Modena variant, as well as p.Asp250His in the literature.  ClinVar contains an entry for this variant (Variation ID: 10372). Experimental studies with purified enzyme extracts have shown that this variant causes partial deficiency of G6PD enzyme activity (PMID: 7806085, 7947239). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000011092 SCV000031319 other G6PD SEATTLE-LIKE 2017-05-24 no assertion criteria provided literature only
OMIM RCV000011093 SCV000031320 other G6PD MODENA 2017-05-24 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.