Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001059211 | SCV001223828 | pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2023-08-02 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 854215). This variant is also known as G6PD Cairo. This missense change has been observed in individual(s) with glucose-6-phosphate dehydrogenase deficiency (PMID: 22906837, 27519946). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 135 of the G6PD protein (p.Asn135Thr). |
Ce |
RCV001091837 | SCV001248071 | pathogenic | not provided | 2023-06-01 | criteria provided, single submitter | clinical testing | G6PD: PM2, PM5, PS3:Moderate, PS4:Moderate, PP1, PP4 |
ARUP Laboratories, |
RCV001091837 | SCV001472687 | pathogenic | not provided | 2023-11-21 | criteria provided, single submitter | clinical testing | The G6PD c.404A>C; p.Asn135Thr variant (rs782322505), also known as c.494A>C; p.Asn165Thr (NM_000402.4) and G6PD Cairo, is reported in the literature in several children with acute hemolytic anemia induced by favism; all affected children demonstrated hyperbilirubinemia and were deficient for G6PD enzyme activity (Al-Sweedan 2012, Beutler 2002, Doss 2016, Reading 2016, Sirdah 2017). This variant is reported in ClinVar (Variation ID: 854215) and is absent from the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. Computational analyses predict that this variant is deleterious (REVEL: 0.887). Based on available information, this variant is considered to be pathogenic. References: Al-Sweedan SA et al. Molecular characterization of glucose-6-phosphate dehydrogenase deficiency among Jordanians. Acta Haematol. 2012 128:195-202. PMID: 22906837. Beutler E et al. Hematologically important mutations: glucose-6-phosphate dehydrogenase. Blood Cells Mol Dis. 2002 28:93-103. PMID: 12064901. Doss CG et al. Genetic Epidemiology of Glucose-6-Phosphate Dehydrogenase Deficiency in the Arab World. Sci Rep. 2016 6:37284. PMID: 27853304. Reading NS et al. Favism, the commonest form of severe hemolytic anemia in Palestinian children, varies in severity with three different variants of G6PD deficiency within the same community. Blood Cells Mol Dis. 2016 60:58-64. PMID: 27519946. Sirdah MM et al. Possible association of 3' UTR +357 A>G, IVS11-nt 93 T>C, c.1311 C>T polymorphism with G6PD deficiency. Hematology. 2017 22:370-374. PMID: 28059001. |
Dunham Lab, |
RCV001059211 | SCV002599329 | pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2022-08-12 | criteria provided, single submitter | curation | Variant found in unrelated hemizygotes with deficiency, anemia, and favism (PS4_M, PP4). Decreased activity in red blood cells (4-20%) (PS3). Predicted to be damaging by SIFT and probably damaging by PolyPhen (PP3). Below expected carrier frequency in gnomAD (PM2). Reported as pathogenic by CeGaT (PP5). Post_P 0.997 (odds of pathogenicity 3155, Prior_P 0.1). |
Revvity Omics, |
RCV001059211 | SCV003822585 | pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2023-05-02 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV003467799 | SCV004195405 | pathogenic | Malaria, susceptibility to | 2023-04-28 | criteria provided, single submitter | clinical testing | |
Breakthrough Genomics, |
RCV001059211 | SCV004243585 | pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2021-07-15 | no assertion criteria provided | clinical testing |