Total submissions: 36
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins NTD LLC |
RCV000079409 | SCV000231598 | pathogenic | not provided | 2017-05-15 | criteria provided, single submitter | clinical testing | |
Courtagen Diagnostics Laboratory, |
RCV000179363 | SCV000236525 | pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2014-02-14 | criteria provided, single submitter | clinical testing | |
UCLA Clinical Genomics Center, |
RCV000179363 | SCV000255508 | likely pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2013-08-13 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000079409 | SCV000321681 | pathogenic | not provided | 2022-05-05 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate decreased enzyme activity in circulating erythrocytes, increased affinity for G6P, and decreased in vitro thermostability (Vulliamy et al., 1998); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 23479361, 27535533, 31152693, 33413378, 31322791, 24460025, 3393536, 27884173, 19594365, 24586352, 1978555, 25548459, 28492530, 8611726, 28492532, 27853304, 27108201, 30097005, 31863082, 33069889, 31019026, 31980526, 34272389, 34426522, 33072997, 33083013, 30755392, 12215013, 32535712, 32860008, 33726816, 1978554, 22906047) |
Invitae | RCV000179363 | SCV000647802 | pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2021-12-19 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 188 of the G6PD protein (p.Ser188Phe). This variant is present in population databases (rs5030868, gnomAD 1.7%). This missense change has been observed in individual(s) with G6PD deficiency (PMID: 1978554, 8611726, 15315792, 16119988, 22018328, 24586352). It is commonly reported in individuals of Mediterranean, Middle Eastern, or Indian ancestry (PMID: 1978554, 8611726, 15315792, 16119988, 22018328, 24586352). ClinVar contains an entry for this variant (Variation ID: 100057). 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. Experimental studies have shown that this missense change affects G6PD function (PMID: 3393536, 22906047, 24460025). For these reasons, this variant has been classified as Pathogenic. |
Counsyl | RCV000179363 | SCV000677998 | pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2015-06-06 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000623137 | SCV000741900 | pathogenic | Inborn genetic diseases | 2016-12-14 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000079409 | SCV000885494 | pathogenic | not provided | 2021-12-21 | criteria provided, single submitter | clinical testing | The G6PD c.563C>T; p.Ser188Phe variant (rs5030868), also known as G6PD Mediterranean, is reported in the literature in multiple individuals affected with hemolytic anemia, hyperbilirubinemia and G6PD deficiency (Hellani 2009, Jamornthanyawat 2014, Kaplan 1997, Moiz 2012, Molou 2014, Vulliamy 1988). Functional analyses of the variant protein shows decreased enzyme activity, increased affinity for G6P and decreased in vitro thermostability (Moiz 2012, Molou 2014, Vulliamy 1988). This variant is reported in ClinVar (Variation ID: 100057). This variant is found predominantly in the South Asian population with an allele frequency of 1.7% (331/19,078 alleles, including 4 homozygotes and 211 hemizygotes) in the Genome Aggregation Database. The serine at codon 188 is moderately conserved, but computational analyses predict that this variant is deleterious (REVEL: 0.811). Based on available information, this variant is considered to be pathogenic. References: Hellani A et al. G6PD Mediterranean S188F codon mutation is common among Saudi sickle cell patients and increases the risk of stroke. Genet Test Mol Biomarkers. 2009 Aug;13(4):449-52. Jamornthanyawat N et al. A population survey of the glucose-6-phosphate dehydrogenase (G6PD) 563C>T (Mediterranean) mutation in Afghanistan. PLoS One. 2014 Feb 21;9(2):e88605. Kaplan M et al. Gilbert syndrome and glucose-6-phosphate dehydrogenase deficiency: a dose-dependent genetic interaction crucial to neonatal hyperbilirubinemia. Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):12128-32. Moiz B et al. Neonatal hyperbilirubinemia in infants with G6PD c.563C > T Variant. BMC Pediatr. 2012 Aug 20;12:126. Molou E et al. Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency in Greek newborns: the Mediterranean C563T mutation screening. Scand J Clin Lab Invest. 2014 Apr;74(3):259-63. Vulliamy TJ et al. Diverse point mutations in the human glucose-6-phosphate dehydrogenase gene cause enzyme deficiency and mild or severe hemolytic anemia. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5171-5. |
Fulgent Genetics, |
RCV000477810 | SCV000893824 | pathogenic | Malaria, susceptibility to; Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000445579 | SCV000915299 | pathogenic | G6PD deficiency | 2018-10-19 | criteria provided, single submitter | clinical testing | Across a selection of the available literature, the G6PD c.563C>T (p.Ser188Phe) variant, also called G6PD Mediterranean, has been identified in a homozygous state in six probands, in a hemizygous state in 109 probands and in a heterozygous state in 25 probands (Hellani et al. 2009; Moiz et al. 2012; Santana et al. 2013; Molou et al. 2014 and Jamornthanyawat et al. 2014). The p.Ser188Phe variant was reported in seven of 42 controls in a presumed heterozygous state and is reported at a frequency of 0.017450 in the South Asian population of the Genome Aggregation Database. The p.Ser188Phe variant resulted in 0-7% residual enzyme activity in red blood cells compared to wild type and caused decreased thermostability and reduced catalytic activity (Vulliamy et al. 1988). Based on the collective evidence, the p.Ser188Phe variant is classified as pathogenic for glucose-6-phosphate dehydrogenase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Mendelics | RCV000179363 | SCV001142109 | pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV000179363 | SCV001150112 | pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2020-01-17 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000079409 | SCV001150542 | pathogenic | not provided | 2022-06-01 | criteria provided, single submitter | clinical testing | |
Centogene AG - |
RCV001250219 | SCV001424421 | pathogenic | G6PD deficient hemolytic anemia | criteria provided, single submitter | clinical testing | ||
Centogene AG - |
RCV000179363 | SCV001426527 | pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | criteria provided, single submitter | clinical testing | ||
Life |
RCV000179363 | SCV001430927 | pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | criteria provided, single submitter | clinical testing | This variant in exon 6 of the G6PD gene results in the amino acid substitution from Serine to Phenylalanine at codon 188 (p.Ser188Phe) with the sequence change of c.653C>T (NM_000402.4). This variant was observed in a proband with decreased level of G6PD enzyme (<2.4 U/dL) which was screened for advanced newborn screening with confirmatory genetic reflex testing at lifecell diagnostics. This variant is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. The reference base is conserved across the species and in-silico predictions by Polyphen and SIFT are damaging. This variant has previously been reported for Anemia, Nonspherocytic Hemolytic, Due to G6pd Deficiency by T J Vulliamy et al., 1988. The Missense Variants Z-Score for this variant is 2.60. Missense Variants Z-Score is produced by the Exome Aggregation Consortium (60,706 adult humans) by computing a signed Z score for the deviation of observed counts from the expected number. Positive Z scores indicate increased constraint (intolerance to variation) and therefore that the gene had fewer missense variants than expected. This variant has been reported six individuals in homozygous condition, in 109 individuals in hemizygous condition and 25 individuals in heterozygous conditions. (Hellani et al. 2009; PMID: 19594365), (Moiz et al. 2012; PMID: 22906047), (Santana et al. 2013; PMID: 23479361), (Molou et al. 2014; PMID: 24460025) and (Jamornthanyawat et al. 2014; PMID: 24586352). | |
Institute of Human Genetics, |
RCV000179363 | SCV001441024 | uncertain significance | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2019-01-01 | criteria provided, single submitter | clinical testing | |
Rady Children's Institute for Genomic Medicine, |
RCV001265539 | SCV001443686 | pathogenic | Hemolytic anemia, G6PD deficient (favism) | 2020-04-14 | criteria provided, single submitter | clinical testing | This variant is also known as c.563C>T, p.Ser188Phe (using the alternative transcripts NM_001042351.3 and NM_001360016.2).This alteration has been previously reported as hemizygous change in patients with hemolytic anemia associated with Glucose 6-phosphate deficiency (PMID: 28067620, 24586352, 11445808, 12768444). Functional studies demonstrate decreased enzyme activity in the circulating erythrocytes of individuals with this variant, increased affinity for G6P and decreased in vitro thermostability (PMID: 9342374, 3393536). It is present in the gnomAD population database at a frequency of 0.23% with 471/204697 in heterozygous state, 6/204697 in homozygous state and 256/204697 in hemizygous state. In silico analyses support a deleterious effect of the c.653C>T (p.Ser218Phe) variant on protein function. Based on the available evidence, the c.653C>T (p.Ser218Phe) variant is classified as Pathogenic. |
Institute of Medical Genetics and Applied Genomics, |
RCV000079409 | SCV001447745 | pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000179363 | SCV001523186 | pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2020-07-27 | criteria provided, single submitter | clinical testing | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
Genome- |
RCV000179363 | SCV001810223 | pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2021-07-22 | criteria provided, single submitter | clinical testing | |
Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV000179363 | SCV002073219 | pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | criteria provided, single submitter | clinical testing | The missense variant p.S188F in G6PD (NM_001042351.2) causes the same amino acid change as a previously established pathogenic variant. This variant is present in population databases (rs5030868, ExAC 1.6%). This variant is the most common cause of G6PD deficiency in the Mediterranean area, the Middle East and the India subcontinent, being reported in 60-96% of biochemically diagnosed individuals (Jamornthanyawat et al., 2014; Molou et al., 2014). Experimental studies show that this variant causes protein instability and results in reduced G6PD enzymatic activity in red blood cells of the patients (Vulliamy et al., 1988). In summary, this variant is the most common G6PD deficiency variant in many populations and has been shown to affect protein activity. For these reasons, this variant has been classified as Pathogenic. | |
Institute of Human Genetics, |
RCV002227060 | SCV002506445 | likely pathogenic | Decreased glucose-6-phosphate dehydrogenase level in blood | 2019-04-01 | criteria provided, single submitter | clinical testing | ACMG categories: PS3,PM1,PP3,PP5,BP1 |
OMIM | RCV000011086 | SCV000031313 | other | G6PD MEDITERRANEAN | 2018-05-11 | no assertion criteria provided | literature only | |
OMIM | RCV000011087 | SCV000031314 | other | G6PD SASSARI | 2018-05-11 | no assertion criteria provided | literature only | |
OMIM | RCV000011088 | SCV000031315 | other | G6PD CAGLIARI | 2018-05-11 | no assertion criteria provided | literature only | |
Firma |
RCV000445579 | SCV000106042 | pathogenic | G6PD deficiency | no assertion criteria provided | clinical testing | ||
Division of Human Genetics, |
RCV000477810 | SCV000536869 | pathogenic | Malaria, susceptibility to; Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2016-05-31 | no assertion criteria provided | research | |
Biochemical Molecular Genetic Laboratory, |
RCV000179363 | SCV000854728 | pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2018-07-14 | no assertion criteria provided | clinical testing | |
Department of Genetics, |
RCV000761429 | SCV000891507 | uncertain significance | Susceptibility to angioedema induced by ACE inhibitors | 2017-12-30 | no assertion criteria provided | curation | |
Clinical Genetics Laboratory, |
RCV001528124 | SCV001739331 | pathogenic | Malaria, susceptibility to | 2021-03-16 | no assertion criteria provided | clinical testing | |
Diagnostic Laboratory, |
RCV000079409 | SCV001741952 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000079409 | SCV001807662 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000079409 | SCV001928877 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000079409 | SCV001976349 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Perkin |
RCV000179363 | SCV002023784 | pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2021-06-09 | no assertion criteria provided | clinical testing |