ClinVar Miner

Submissions for variant NM_001360016.2(G6PD):c.1347G>C (p.Gln449His)

gnomAD frequency: 0.00001  dbSNP: rs1557229572
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001231280 SCV001403796 pathogenic Anemia, nonspherocytic hemolytic, due to G6PD deficiency 2022-11-23 criteria provided, single submitter clinical testing 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. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 958165). This missense change has been observed in individual(s) with glucose-6-phosphate dehydrogenase deficiency (PMID: 10782016). This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 449 of the G6PD protein (p.Gln449His). This variant is present in population databases (no rsID available, gnomAD 0.001%).
Dunham Lab, University of Washington RCV001231280 SCV002599285 likely 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 favism (PP4, PS4_M). Decreased activity in red blood cells (2-48%) (PS3). Below expected carrier frequency in gnomAD (PM2). Post_P 0.988 (odds of pathogenicity 729.3, Prior_P 0.1).
Baylor Genetics RCV003462786 SCV004195395 pathogenic Malaria, susceptibility to 2024-03-23 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV005232196 SCV005877734 likely pathogenic not provided 2024-01-30 criteria provided, single submitter clinical testing The G6PD c.1347G>C; p.Gln449His variant (rs1557229572), also known as G6PD Cassano, is reported in the literature in several individuals affected with G6PD deficiency (Alfinito 1997, Barisic 2005, Calabro 1993). This variant is also reported in ClinVar (Variation ID: 958165). This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. Functional analyses of the variant protein show a reduction in enzyme activity and altered kinetics (Calabro 1993). Computational analyses predict that this variant is deleterious (REVEL: 0.836). Based on available information, this variant is considered to be likely pathogenic. References: Alfinito F et al. Molecular characterization of G6PD deficiency in Southern Italy: heterogeneity, correlation genotype-phenotype and description of a new variant (G6PD Neapolis). Br J Haematol. 1997 Jul. PMID: 9233561. Barisic M et al. Characterization of G6PD deficiency in southern Croatia: description of a new variant, G6PD Split. J Hum Genet. 2005 PMID: 16143877. Calabro V et al. Genetic heterogeneity of glucose-6-phosphate dehydrogenase deficiency revealed by single-strand conformation and sequence analysis. Am J Hum Genet. 1993 Mar. PMID: 8447319.

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