ClinVar Miner

Submissions for variant NM_002055.5(GFAP):c.716G>T (p.Arg239Leu)

dbSNP: rs59565950
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India RCV000192137 SCV002522652 pathogenic Alexander disease criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000056901 SCV003441992 pathogenic not provided 2022-02-18 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 239 of the GFAP protein (p.Arg239Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Alexander disease (PMID: 17043438, 21041050, 34146839). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 66498). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant disrupts the p.Arg239 amino acid residue in GFAP. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11138011, 11587071). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.
Epithelial Biology; Institute of Medical Biology, Singapore RCV000056901 SCV000088014 not provided not provided no assertion provided not provided
GeneReviews RCV000192137 SCV000223000 not provided Alexander disease no assertion 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.