ClinVar Miner

Submissions for variant NM_001164277.2(SLC37A4):c.1179G>A (p.Trp393Ter)

gnomAD frequency: 0.00002  dbSNP: rs902775927
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001192958 SCV001361447 pathogenic Glucose-6-phosphate transport defect 2019-10-11 criteria provided, single submitter clinical testing Variant summary: SLC37A4 c.1179G>A (p.Trp393X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 1.6e-05 in 249216 control chromosomes (gnomAD). c.1179G>A has been reported in the literature in multiple individuals affected with Glycogen Storage Disease Type Ib (Choi_2017, Hiraiwa_1999, Prasad_2017, Santer_2000). These data indicate that the variant is very likely to be associated with disease. A functional study, Chen_2000, found the variant caused little to no SLC37A4 [referred to as G6PT (legacy name)] synthesis to occur. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001192958 SCV001592184 pathogenic Glucose-6-phosphate transport defect 2023-04-18 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the SLC37A4 protein in which other variant(s) (p.Arg415*) have been determined to be pathogenic (PMID: 10482962, 10931421, 15059622, 21575371). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 928687). This variant is also known as 1348G>A. This premature translational stop signal has been observed in individual(s) with clinical features of glycogen storage disease type Ib (PMID: 10923042, 29119402). This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Trp393*) in the SLC37A4 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 37 amino acid(s) of the SLC37A4 protein.
Baylor Genetics RCV001192958 SCV004202453 pathogenic Glucose-6-phosphate transport defect 2024-01-16 criteria provided, single submitter clinical testing
Natera, Inc. RCV001192958 SCV002078563 pathogenic Glucose-6-phosphate transport defect 2020-03-30 no assertion criteria provided clinical testing

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