ClinVar Miner

Submissions for variant NM_001164277.1(SLC37A4):c.1015G>T (p.Gly339Cys) (rs80356490)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000059116 SCV000252293 pathogenic not provided 2016-09-28 criteria provided, single submitter clinical testing p.Gly339Cys (GGT>TGT): c.1015 G>T in exon 9 of the SLC37A4 gene (NM_001164277.1) A variant of unknown significance has been identified in the SLC37A4 gene.The G339C missense mutation in the SLC37A4 gene has been reported previously in association with glycogen storage disease type Ib (Gerin et al., 1997). Furthermore, functional studies showed that when a transfected cell carried the G339C mutation, the SLC37A4 enzyme activity was undetectable (Chen et al., 2000). The variant is found in MITONUC-MITOP panel(s).
Invitae RCV000007330 SCV000817446 pathogenic Glucose-6-phosphate transport defect 2018-06-22 criteria provided, single submitter clinical testing This sequence change replaces glycine with cysteine at codon 339 of the SLC37A4 protein (p.Gly339Cys). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and cysteine. This variant is present in population databases (rs80356490, ExAC 0.02%). This variant has been observed to be homozygous or in combination with another SLC37A4 variant in individuals affected with glycogen storage disease (PMID: 9428641, 9758626, 10923042, 10482962). This variant is described as a possible founder mutation of middle European ancestry (PMID: 10923042). This variant is also known as c.1184G>T in the literature. ClinVar contains an entry for this variant (Variation ID: 6921). Experimental studies have shown that this missense change abolishes microsomal G6P uptake activity and destabilized the glucose-6-phosphate transporter protein (PMID: 12444104). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000007330 SCV000920218 pathogenic Glucose-6-phosphate transport defect 2017-11-09 criteria provided, single submitter clinical testing Variant summary: The SLC37A4 c.1015G>T (p.Gly339Cys) variant causes a missense change located in the Major facilitator superfamily domain (IPR020846) (InterPro) involving the alteration of a conserved nucleotide. 3/3 in silico tools predict a damaging outcome for this variant. Functional studies showed that this variant is associated with 4.9% of the microsomal G6P wildtype uptake activity and 5.1% of the WT Pi uptake activity in proteoliposomes (Chen_2002, Chen_2008). This variant was found in 20/272082 control chromosomes in gnomAD at a frequency of 0.0000735, which does not exceed the estimated maximal expected allele frequency of a pathogenic SLC37A4 variant (0.0012247). This variant was reported in multiple patients with GSD types Ib and Ic in compound heterozygotes and homozygotes (Veiga-da-Cunha_1998). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
OMIM RCV000007330 SCV000027528 pathogenic Glucose-6-phosphate transport defect 1997-12-15 no assertion criteria provided literature only
GeneReviews RCV000007330 SCV000040884 pathogenic Glucose-6-phosphate transport defect 2016-08-25 no assertion criteria provided literature only
UniProtKB/Swiss-Prot RCV000059116 SCV000090645 not provided not provided no assertion provided not provided
Counsyl RCV000007330 SCV000678140 pathogenic Glucose-6-phosphate transport defect 2015-06-06 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.