ClinVar Miner

Submissions for variant NM_033380.3(COL4A5):c.3427G>A (p.Gly1143Ser)

dbSNP: rs104886228
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Gharavi Laboratory,Columbia University RCV000681895 SCV000809374 likely pathogenic not provided 2018-09-16 criteria provided, single submitter research
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota RCV000021509 SCV000889954 pathogenic X-linked Alport syndrome 2017-02-23 criteria provided, single submitter clinical testing
Invitae RCV000681895 SCV001222920 pathogenic not provided 2021-12-20 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1143 of the COL4A5 protein (p.Gly1143Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with X-linked dominant Alport syndrome (PMID: 7969679). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 24630). 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) performed at Invitae indicates that this missense variant is expected to disrupt COL4A5 protein function. This variant disrupts the triple helix domain of COL4A5. 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.
Institute of Human Genetics, University of Leipzig Medical Center RCV000021509 SCV001429110 likely pathogenic X-linked Alport syndrome 2017-12-12 criteria provided, single submitter clinical testing
GeneDx RCV000681895 SCV001982247 pathogenic not provided 2021-09-28 criteria provided, single submitter clinical testing Reported in multiple individuals with Alport syndrome belonging to a single family in published literature (Renieri et al., 1994; Renieri et al., 1996); however, data is limited; Affects a glycine residue in a Gly-X-Y motif in the triple helical region of the COL4A5 gene, where the majority of pathogenic missense variants occur, and is predicted to disrupt normal protein folding and function (Stenson et al., 2014; Jais et al., 2000); Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25525159, 8651296, 24077912, 7969679)
CeGaT Center for Human Genetics Tuebingen RCV000681895 SCV002564125 pathogenic not provided 2020-09-01 criteria provided, single submitter 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.