ClinVar Miner

Submissions for variant NM_002055.5(GFAP):c.230A>G (p.Asn77Ser)

dbSNP: rs57590980
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000056865 SCV002201302 pathogenic not provided 2024-04-03 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 77 of the GFAP protein (p.Asn77Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Alexander disease (PMID: 15732097, 17894839, 26478912). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 66468). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GFAP protein function. This variant disrupts the p.Asn77 amino acid residue in GFAP. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23364391). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Epithelial Biology; Institute of Medical Biology, Singapore RCV000056865 SCV000087978 not provided not provided no assertion provided not provided
GeneReviews RCV000192107 SCV000222963 not provided Alexander disease no assertion provided literature only
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City RCV000192107 SCV001469164 pathogenic Alexander disease 2020-02-05 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.