Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Foundation for Research in Genetics and Endocrinology, |
RCV001257425 | SCV001429642 | uncertain significance | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2020-07-02 | criteria provided, single submitter | clinical testing | A heterozygous missense variation in exon 9 of the G6PD gene that results in the amino acid substitution of Lysine for Glutamic acid at codon 317 was detected. The observed variant has previously been reported in patients affected with G6PD deficiency (Sukumar et al. 2004, Ahluwalia et al. 1992) and lies in the glucose-6-phosphate dehydrogenase, C-terminal domain of the G6PD protein. This variant is a prevalent G6PD variant in the South Asian population, typically associated with partial reduction of enzyme activity. The variant c.949G>A (p.Glu317Lys) has a minor allele frequency of 0.2% and 0.1% in the 1000 genomes and gnomAD databases respectively. The in silico prediction of the variant are possibly damaging by PolyPhen-2 (HumDiv) and damaging by LRT. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as a variant of uncertain significance. |
| Invitae | RCV001257425 | SCV004408194 | uncertain significance | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2023-02-05 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 287 of the G6PD protein (p.Glu287Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with G6PD-related conditions. ClinVar contains an entry for this variant (Variation ID: 431774). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |