ClinVar Miner

Submissions for variant NM_001164277.1(SLC37A4):c.1179G>A (p.Trp393Ter)

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Total submissions: 2
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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.
Invitae RCV001192958 SCV001592184 pathogenic Glucose-6-phosphate transport defect 2020-08-27 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the SLC37A4 gene (p.Trp393*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 37 amino acids of the SLC37A4 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of glycogen storage disease type Ib (PMID: 10923042, 29119402). This variant is also known as 1348G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 928687). This variant disrupts the C-terminus of the SLC37A4 protein. Other variant(s) that disrupt this region (p.Arg415*) have been determined to be pathogenic (PMID: 10931421, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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