ClinVar Miner

Submissions for variant NM_000402.4(G6PD):c.727G>T (p.Val243Leu)

dbSNP: rs137852326
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000790819 SCV000231599 pathogenic not provided 2012-08-21 criteria provided, single submitter clinical testing
Courtagen Diagnostics Laboratory, Courtagen Life Sciences RCV000066251 SCV000236517 pathogenic Anemia, nonspherocytic hemolytic, due to G6PD deficiency 2014-08-28 criteria provided, single submitter clinical testing
Invitae RCV000066251 SCV001235829 likely pathogenic Anemia, nonspherocytic hemolytic, due to G6PD deficiency 2022-01-26 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. 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: 10383). This variant is also known as G6PD Gastonia. This missense change has been observed in individual(s) with glucose-6-phosphate dehydrogenase deficiency (PMID: 1805484, 1999409; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 213 of the G6PD protein (p.Val213Leu).
Mayo Clinic Laboratories, Mayo Clinic RCV000790819 SCV001715687 likely pathogenic not provided 2019-12-16 criteria provided, single submitter clinical testing PS4_moderate, PM1, PM2, PP5, BP4
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000790819 SCV002050010 pathogenic not provided 2021-11-24 criteria provided, single submitter clinical testing The G6PD c.637G>T; p.Val213Leu variant (rs137852326), also known as G6PD Marion, G6PD Gastonia and G6PD Minnesota, is reported in the literature in individuals with G6PD deficiency and nonspherocytic hemolytic anemia (Buetler 1991). In addition, this variant has also been reported in an infant with severe hyperbilirubinemia and cholestasis in conjunction with G6PD Cincinnati (Mizukawa 2011). Functional analyses of the variant protein show a significant reduction in enzymatic activity (Buetler 1991). This variant is also reported in ClinVar (Variation ID: 10383). This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. The valine at codon 213 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.688). Considering available information, this variant is classified as a class I pathogenic variant. References: Beutler E et al. DNA sequence abnormalities of human glucose-6-phosphate dehydrogenase variants. J Biol Chem. 1991 Mar 5;266(7):4145-50. Mizukawa B et al. Cooperating G6PD mutations associated with severe neonatal hyperbilirubinemia and cholestasis. Pediatr Blood Cancer. 2011 May;56(5):840-2.
Institute of Human Genetics, University Hospital Muenster RCV002287328 SCV002577776 likely pathogenic Abnormal circulating glucose-6-phosphate dehydrogenase concentration 2021-12-08 criteria provided, single submitter clinical testing ACMG categories: PS3,PM2,PP2,PP3,BP1
Dunham Lab, University of Washington RCV000066251 SCV002599341 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). Decreased activity in red blood cells (3-9%) (PS3). Below expected carrier frequency in gnomAD (PM2). Reported as pathogenic by multiple clinical testing groups (PP5). Post_P 0.994 (odds of pathogenicity 1517, Prior_P 0.1).
Revvity Omics, Revvity RCV000066251 SCV003820099 pathogenic Anemia, nonspherocytic hemolytic, due to G6PD deficiency 2022-09-08 criteria provided, single submitter clinical testing
OMIM RCV000011110 SCV000031337 other G6PD GASTONIA 2017-05-24 no assertion criteria provided literature only
OMIM RCV000011111 SCV000031338 other G6PD MARION 2017-05-24 no assertion criteria provided literature only
OMIM RCV000011112 SCV000031339 other G6PD MINNESOTA 2017-05-24 no assertion criteria provided literature only
OMIM RCV000066251 SCV000105928 pathogenic Anemia, nonspherocytic hemolytic, due to G6PD deficiency 1990-12-01 no assertion criteria provided literature only

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