ClinVar Miner

Submissions for variant NM_005629.4(SLC6A8):c.259G>A (p.Gly87Arg)

dbSNP: rs122453115
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel, ClinGen RCV000012466 SCV004042591 uncertain significance Creatine transporter deficiency 2023-08-24 reviewed by expert panel curation The NM_005629.4:c.259G>A variant in SLC6A8 is a missense variant predicted to cause substitution of glycine by arginine at amino acid 87 (p.Gly87Arg). This variant is absent in population databases (PM2_Supporting) and has been described in the literature in an individual for whom biochemical testing could not be performed (PMID: 15154114). The computational predictor REVEL gives a score of 0.961 which is above the thresholds predicting a damaging (>0.75) impact on SLC6A8 function (PP3). When fibroblasts deficient for this SLC6A8 variant were grown in the presence of a physiological Cr concentration (25uM), the average creatine uptake was just above the detection limit, whereas in the control fibroblasts it was significantly higher (PMID: 17465020) (PS3_Supporting). There is a ClinVar entry for this variant (Variation ID:11700). In summary, this variant meets the criteria to be classified as a Variant of Uncertain Significance for Creatine Transporter Deficiency. SLC6A8-specific ACMG/AMP criteria applied, as specified by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel (Specifications Version 1.1.0): PP3, PS3_Supporting, PM2_Supporting. (Classification approved by the ClinGen CCDS VCEP, July 13, 2023)
Mayo Clinic Laboratories, Mayo Clinic RCV001508970 SCV001715424 likely pathogenic not provided 2020-06-24 criteria provided, single submitter clinical testing PS3, PM2, PP3, PM6
OMIM RCV000012466 SCV000032700 pathogenic Creatine transporter deficiency 2004-07-01 no assertion criteria provided literature only

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.