ClinVar Miner

Submissions for variant NM_001360016.2(G6PD):c.1004C>A (p.Ala335Asp)

gnomAD frequency: 0.00001  dbSNP: rs1557229854
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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 RCV001379702 SCV001577550 likely pathogenic Anemia, nonspherocytic hemolytic, due to G6PD deficiency 2020-03-29 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Ala335 amino acid residue in G6PD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11499668, 16927025, 20602793, 21677401, 22293322, 25548459, 2606066). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with glucose-6-phosphate dehydrogenase deficiency (PMID: 5775246, 15625830, 7803800). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with aspartic acid at codon 335 of the G6PD protein (p.Ala335Asp). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and aspartic acid.
Dunham Lab, University of Washington RCV001379702 SCV002599354 pathogenic Anemia, nonspherocytic hemolytic, due to G6PD deficiency 2022-08-12 criteria provided, single submitter curation Variant found in unrelated hemizygotes with deficiency, some with anemia (PS4_M, PP4). Decreased activity in red blood cells (11-19%) (PS3). Affects same amino acid as pathogenic 335A>T (ClinVar ID 10363) (PM5). Below expected carrier frequency in gnomAD (PM2). Post_P 0.997 (odds of pathogenicity 3158, Prior_P 0.1).
Baylor Genetics RCV003469642 SCV004195401 likely pathogenic Malaria, susceptibility to 2023-05-18 criteria provided, single submitter clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc RCV004796619 SCV005416074 pathogenic Malaria, susceptibility to; Anemia, nonspherocytic hemolytic, due to G6PD deficiency criteria provided, single submitter clinical testing PM2_Supporting+PS4+PP4+PS3_Moderate+PM5

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