ClinVar Miner

Submissions for variant NM_001360016.2(G6PD):c.1192G>A (p.Glu398Lys)

dbSNP: rs137852325
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000991012 SCV001142103 pathogenic Anemia, nonspherocytic hemolytic, due to G6PD deficiency 2019-05-28 criteria provided, single submitter clinical testing
Dunham Lab, University of Washington RCV000991012 SCV002599372 pathogenic Anemia, nonspherocytic hemolytic, due to G6PD deficiency 2022-08-12 criteria provided, single submitter curation Variant found in unrelated hemizygotes with deficiency and CNSHA (PS4_M, PP4). In one family, heizygous brothers both have deficiency CNSHA, and mother is heterozygous (PP1). Undetectable activity in red blood cells (PS3). Within dimer interface (PM1). Not found in gnomAD (PM2). Reported as pathogenic by Mendelics (PP5). Post_P 0.999 (odds of pathogenicity 13661, Prior_P 0.1).
Neuberg Centre For Genomic Medicine, NCGM RCV000991012 SCV005373641 pathogenic Anemia, nonspherocytic hemolytic, due to G6PD deficiency 2023-05-20 criteria provided, single submitter clinical testing The observed missense variant c.1192G>A(p.Glu398Lys) in the G6PD gene has been reported previously in individual(s) with G6PD deficiency (Tong Y, et al., 2020). This variant is located in a mutational hot spot. A different amino acid change [c.1193A>G (p.Glu398Gly)] at the same position has been submitted to ClinVar as likely pathogenic. This variant is absent in the gnomAD Exomes. This variant has been reported to the ClinVar database as Pathogenic. The amino acid Glutamic acid at position 398 is changed to a Lysine changing protein sequence and it might alter its composition and physico-chemical properties. Multiple lines of computational evidence (Polyphen - Possibly damaging, SIFT – Damaging and MutationTaster - Disease causing) predict a damaging effect on protein structure and function for this variant. The residue is conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic.

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