ClinVar Miner

Submissions for variant NM_000402.4(G6PD):c.1114C>T (p.Leu372Phe)

gnomAD frequency: 0.00003  dbSNP: rs137852342
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000079389 SCV000111268 uncertain significance not provided 2012-12-17 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000079389 SCV000885493 likely pathogenic not provided 2017-07-28 criteria provided, single submitter clinical testing
Mendelics RCV000991013 SCV001142104 uncertain significance Anemia, nonspherocytic hemolytic, due to G6PD deficiency 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV000991013 SCV001513322 uncertain significance Anemia, nonspherocytic hemolytic, due to G6PD deficiency 2021-08-12 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 342 of the G6PD protein (p.Leu342Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. This missense change has been observed in individual(s) with glucose-6-phosphate dehydrogenase deficiency (PMID: 8364584, 10502785, 16329560, 20203002, 30045279, 30315739). This variant is also known as C13184T or Chinese-5. ClinVar contains an entry for this variant (Variation ID: 10405). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Dunham Lab, University of Washington RCV000991013 SCV002599355 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). Also found in two heterozygous sisters with deficiency who inherited this variant (c.1024C>T) from father and c.383T>C from mother (PP1). Decreased activity in red blood cells (2-39%) (PS3). Below expected carrier frequency in gnomAD (PM2). Post_P 0.994 (odds of pathogenicity 1517, Prior_P 0.1).
Revvity Omics, Revvity RCV000991013 SCV003833854 likely pathogenic Anemia, nonspherocytic hemolytic, due to G6PD deficiency 2023-12-21 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004526593 SCV005040243 pathogenic Niemann-Pick disease, type C 2024-03-15 criteria provided, single submitter clinical testing Variant summary: NPC1 c.1114C>T (p.Arg372Trp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251162 control chromosomes. c.1114C>T has been reported in the literature in individuals affected with Niemann-Pick Disease Type C. These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004540994 SCV005040778 pathogenic Metachromatic leukodystrophy 2024-03-15 criteria provided, single submitter clinical testing Variant summary: ARSA c.1114C>T (p.Arg372Trp) results in a non-conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250080 control chromosomes. c.1114C>T has been reported in the literature in multiple individuals affected with Metachromatic Leukodystrophy (Biffi_2008, Heinisch_1995, Fumagalli_2021). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000011148 SCV000031375 other G6PD MAHIDOL-LIKE 2013-04-18 no assertion criteria provided literature only

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