ClinVar Miner

Submissions for variant NM_001164277.1(SLC37A4):c.59G>A (p.Gly20Asp) (rs193302881)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000699431 SCV000920222 pathogenic Glucose-6-phosphate transport defect 2018-08-27 criteria provided, single submitter clinical testing Variant summary: SLC37A4 c.59G>A (p.Gly20Asp) results in a non-conservative amino acid change located in the Major facilitator superfamily domain (IPR020846) of the encoded protein sequence. Two of two in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.4e-05 in 276916 control chromosomes (gnomAD). c.59G>A has been reported in the literature in multiple individuals affected with Glycogen Storage Disease Type Ib and Type Ic (Veiga-da-Cunha 1998, Galli 1999, Jun 2014). 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 (Chen 2002). The most pronounced variant effect results in <10% of normal microsomal G6P uptake activity. 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 RCV000699431 SCV000828142 likely pathogenic Glucose-6-phosphate transport defect 2018-04-09 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 20 of the SLC37A4 protein (p.Gly20Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with glycogen-storage disease type Ib (GSD Ib) (PMID: 9758626, 12373566, 10518030). ClinVar contains an entry for this variant (Variation ID: 68286). Experimental studies have shown that this missense change disrupts the activity and microsomal uptake of glucose-6-phosphatase (PMID: 12444104). 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.
UniProtKB/Swiss-Prot RCV000059137 SCV000090666 not provided not provided no assertion provided not provided

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