ClinVar Miner

Submissions for variant NM_000402.4(G6PD):c.682C>T (p.Arg228Cys) (rs137852330)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000991015 SCV001142108 uncertain significance Anemia, nonspherocytic hemolytic, due to G6PD deficiency 2019-05-28 criteria provided, single submitter clinical testing
LifeCell International Pvt. Ltd RCV000991015 SCV001443092 pathogenic Anemia, nonspherocytic hemolytic, due to G6PD deficiency criteria provided, single submitter clinical testing This variant in exon 6 of the G6PD gene results in the amino acid substitution from Arginine to Cystine at codon 228 (p.Arg228Cys) with the sequence change of c.682C>T (NM_000402.4). This variant was observed in a proband with decreased level of G6PD enzyme (<2.4 U/dL) which was screened for advanced newborn screening with confirmatory genetic reflex testing at Lifecell diagnostics. The observed variant has a minor allele frequency of 0.0000327% in gnomAD database. The reference base is conserved across the species and in-silico predictions by Polyphen and SIFT are damaging. This is a Class II variant associated with moderate G6PD deficiency (<10% activity), with intermittent hemolysis. The G6PD c.682C>T; p.Arg228Cys variant, also referred to as c.592C>T; p.Arg198Cys, commonly known as G6PD-Coimbra or Shunde or Vancouver in the literature. This variant has previously been reported for Glucose-6- phosphate dehydrogenase (G6PD) deficiency by (He Y et al., 2020 PMID: 33051526; Islam MT et al., 2018 PMID: 30097005; Lee J et al., 2018 PMID: 29548282)
Invitae RCV000991015 SCV001586055 pathogenic Anemia, nonspherocytic hemolytic, due to G6PD deficiency 2020-01-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 198 of the G6PD protein (p.Arg198Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs137852330, ExAC 0.02%). This variant has been observed in individual(s) with G6PD-related conditions (PMID: 11499668, 16927025, 7789945, 16155737, 1551674). This variant is also known as G6PD Coimbra. ClinVar contains an entry for this variant (Variation ID: 10391, 10392). This variant has been reported to affect G6PD protein function (PMID: 8118045). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000011126 SCV000031353 other G6PD COIMBRA 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.