ClinVar Miner

Submissions for variant NM_000091.5(COL4A3):c.3546_3548dup (p.Gly1183dup)

dbSNP: rs1175052474
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000626593 SCV000747294 pathogenic Proteinuria; Microscopic hematuria; Moderate albuminuria 2017-01-01 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000626594 SCV000747295 likely pathogenic Macroscopic hematuria 2017-01-01 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000505632 SCV001369701 pathogenic Autosomal dominant Alport syndrome 2019-10-11 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM1,PM2,PM4.
Invitae RCV000681705 SCV001485870 likely pathogenic not provided 2024-01-08 criteria provided, single submitter clinical testing This variant, c.3546_3548dup, results in the insertion of 1 amino acid(s) of the COL4A3 protein (p.Gly1183dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with Alport syndrome (PMID: 30586318; Invitae). ClinVar contains an entry for this variant (Variation ID: 438655). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneDx RCV000681705 SCV001983267 uncertain significance not provided 2021-10-26 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In-frame insertion of 1 amino acid in a non-repeat region; Has not been previously published as pathogenic or benign to our knowledge
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000505632 SCV002764995 likely pathogenic Autosomal dominant Alport syndrome 2022-07-28 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003915403 SCV004732621 likely pathogenic COL4A3-related disorder 2024-02-14 criteria provided, single submitter clinical testing The COL4A3 c.3546_3548dupAGG variant is predicted to result in an in-frame duplication (p.Gly1183dup). This variant has been reported in the heterozygous state in an individual with glomerulopathy (Table S7, Groopman et al. 2019. PubMed ID: 30586318). In addition, at PreventionGenetics, we have previously found this variant in the heterozygous state in an individual tested for the nephrotic syndrome and focal segmental glomerulosclerosis (FSGS) panel. This one amino acid duplication variant occurs at the conserved triple helical domain (residues 43-1438) of the COL4A3 protein (uniprot.org), where substitutions of the glycine (Gly) residue are usually pathogenic (Hudson et al. 1993. PubMed ID: 8253711; https://www.ncbi.nlm.nih.gov/books/NBK1207/). The consequence of this glycine duplication variant is expected to disturb the conserved triple helical Gly-X-Y repeats; and the same type of one amino acid duplication/insertion variant at a different but nearby location has been reported in an individual with isolated hematuria (c.3547_3548insGGA resulting in p.Gly1183_Asn1184insArg at Slajpah et al. 2007. PubMed ID: 17396119). The p.Gly1183dup variant is interpreted as likely pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV000681705 SCV004811563 likely pathogenic not provided 2024-03-01 criteria provided, single submitter clinical testing COL4A3: PM1, PM2, PM4:Supporting, PS4:Supporting
Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare RCV000505632 SCV000599808 pathogenic Autosomal dominant Alport syndrome 2019-10-31 no assertion criteria provided clinical testing
Gharavi Laboratory, Columbia University RCV000681705 SCV000809157 likely pathogenic not provided 2018-09-16 no assertion criteria provided research
Natera, Inc. RCV001834631 SCV002076419 uncertain significance Alport syndrome 2020-03-03 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.