Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000991014 | SCV001142107 | pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Dunham Lab, |
RCV000991014 | SCV002599340 | pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2022-08-12 | criteria provided, single submitter | curation | Variant found in unrelated hemizygotes with deficiency (PS4_M, PP4). In one family, hemizygote son has deficiency, heterozygous mother has decreased G6PD activity (PP1); in another family, hemizygote son inherited variant from heterozygote mother, but neither maternal grandparent has variant, suggesting de novo (PM6). Decreased activity in red blood cells (1%) and when expressed in yeast (60%) (PS3). Located in substrate binding site (PM1). Not found in gnomAD (PM2). Reported as pathogenic by Mendelics (PP5). Post_P 0.9998 (odds of pathogenicity 59154, Prior_P 0.1). |
| Invitae | RCV000991014 | SCV004299714 | pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2023-07-15 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg198 amino acid residue in G6PD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1551674, 7789945, 11499668, 16155737, 16927025). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 198 of the G6PD protein (p.Arg198His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with glucose-6-phosphate dehydrogenase deficiency (PMID: 18043863, 29333274). ClinVar contains an entry for this variant (Variation ID: 10417). 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. |
| OMIM | RCV000011161 | SCV000031388 | other | G6PD NILGIRI | 2017-05-24 | no assertion criteria provided | literature only |