Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001854231 | SCV002279338 | likely pathogenic | Glucose-6-phosphate transport defect | 2021-09-08 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 68 of the SLC37A4 protein (p.Gly68Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with glycogen storage disease (PMID: 9758626, 11949931, 12373566, 15906092). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as 371G>A. ClinVar contains an entry for this variant (Variation ID: 68275). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this missense change affects SLC37A4 function (PMID: 10940311, 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001854231 | SCV003844702 | pathogenic | Glucose-6-phosphate transport defect | 2023-02-14 | criteria provided, single submitter | clinical testing | Variant summary: SLC37A4 c.202G>A (p.Gly68Arg) 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 was absent in 232006 control chromosomes. c.202G>A has been reported in the literature in individuals affected with Glycogen Storage Disease Type Ib. These data indicate that the variant is likely to be associated with disease (Example: Veiga_1998, Beegle_2015, Galli_1999, Jun_2014 et.) . Two publications report experimental evidence indicating a severe decrease in in microsomal G6P activity, 8.1% of Wildtype (Chen_2000, Chen2002). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Uni |
RCV000059125 | SCV000090654 | not provided | not provided | no assertion provided | not provided |