Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000821638 | SCV000962407 | pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 131 of the G6PD protein (p.Gly131Val). This variant is present in population databases (rs137852341, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with G6PD deficiency (PMID: 11243133, 11400791, 25775246). It is commonly reported in individuals of South East Asian ancestry (PMID: 11243133, 11400791, 25775246). This variant is also known as the Quing Yuan or Chinese-4 variant. ClinVar contains an entry for this variant (Variation ID: 10404). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
Mendelics | RCV000821638 | SCV001142112 | pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2022-05-27 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV001810843 | SCV002047725 | pathogenic | not provided | 2021-05-18 | criteria provided, single submitter | clinical testing | The G6PD c.392G>T; p.Gly131Val variant (rs137852341), also known as Chinese-4, is described in the literature in several individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency (Chiu 1993, Peng 2015. Additionally, this variant displays only 20 percent enzymatic activity compared to the wildtype protein (Chiu 1993), and is considered a class III variant (Fu 2018). This variant is also reported in ClinVar (Variation ID: 10404), and is found in the East Asian population with an allele frequency of 0.10% (15/14841 alleles, including 3 hemizygotes) in the Genome Aggregation Database. The glycine residue is moderately conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.855). Based on available information, this variant is considered to be pathogenic. References: Chiu DT et al. Molecular characterization of glucose-6-phosphate dehydrogenase (G6PD) deficiency in patients of Chinese descent and identification of new base substitutions in the human G6PD gene. Blood. 1993 81(8):2150-4. PMID: 8471773. Fu C et al. Newborn screening of glucose-6-phosphate dehydrogenase deficiency in Guangxi, China: determination of optimal cutoff value to identify heterozygous female neonates. Sci Rep. 2018 Jan 16;8(1):833. PMID: 29339739. Peng Q et al. Large cohort screening of G6PD deficiency and the mutational spectrum in the Dongguan District in Southern China. PLoS One. 2015 10(3):e0120683. PMID: 25775246. |
Dunham Lab, |
RCV000821638 | SCV002599306 | pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2022-08-12 | criteria provided, single submitter | curation | Variant found in unrelated hemizygotes with G6PD deficiency, some with anemia (PP4, PS4_M). Decreased activity in red blood cells of hemizygotes (0-49%) (PS3). Predicted to be deleterious by REVEL and probably damaging by PolyPhen (PP3). Below expected carrier frequency in gnomAD (PM2). Post_P 0.994 (odds of pathogenicity 1517, Prior_P 0.1). |
Fulgent Genetics, |
RCV002496324 | SCV002811109 | pathogenic | Malaria, susceptibility to; Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2021-07-24 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000821638 | SCV003833809 | likely pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2023-04-22 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV003460457 | SCV004195380 | likely pathogenic | Malaria, susceptibility to | 2024-03-30 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000011147 | SCV000031374 | other | G6PD QUING YUAN | 2013-04-18 | no assertion criteria provided | literature only |