ClinVar Miner

Submissions for variant NM_000495.5(COL4A5):c.2288G>A (p.Gly763Glu) (rs281874689)

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
Center of Genomic medicine, Geneva,University Hospital of Geneva RCV000021382 SCV000537722 pathogenic Alport syndrome 1, X-linked recessive 2014-08-27 criteria provided, single submitter clinical testing
Invitae RCV001067665 SCV001232735 pathogenic not provided 2020-07-14 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 763 of the COL4A5 protein (p.Gly763Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Alport syndrome (PMID: 20378821, 27353043, Invitae). ClinVar contains an entry for this variant (Variation ID: 24503). Glycine residues within the Gly-Xaa-Yaa repeats of the triple helix domain are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236). In COL4A5, missense variants at these glycine residues are significantly enriched in individuals with disease (PMID: 23720012, 27627812) compared to the general population (ExAC). For these reasons, this variant has been classified as Pathogenic.
Precision Medicine Center,Zhengzhou University RCV000021382 SCV001593037 likely pathogenic Alport syndrome 1, X-linked recessive criteria provided, single submitter research PM1:Located in a mutational hot spot PM2:not found in gnomAD PP2:Missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease PP3:Multiple lines of computational evidence support a deleterious effect on the gene or gene product PP4:Patient's phenotype is highly specific for a disease
Research and Development, ARUP Laboratories RCV000021382 SCV000042048 moderate Alport syndrome 1, X-linked recessive 2012-12-04 no assertion criteria provided clinical testing Converted during submission to Pathogenic.

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.