ClinVar Miner

Submissions for variant NM_001845.6(COL4A1):c.2263G>A (p.Gly755Arg)

dbSNP: rs672601346
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
Athena Diagnostics Inc RCV000710799 SCV000841103 pathogenic not provided 2018-05-14 criteria provided, single submitter clinical testing
Mendelics RCV000989163 SCV001139382 pathogenic Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000710799 SCV001748409 pathogenic not provided 2021-04-01 criteria provided, single submitter clinical testing
Invitae RCV000710799 SCV002237770 pathogenic not provided 2023-02-25 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with clinical features of hereditary angiopathy with nephropathy, aneurysms and muscle cramps (PMID: 19477666, 20385946, 20733150). In at least one individual the variant was observed to be de novo. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 755 of the COL4A1 protein (p.Gly755Arg). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 161974). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the triple helix domain of COL4A1. 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 COL4A1 variants affecting these glycine residues are significantly enriched in individuals with disease (PMID: 9016532, 17078022) compared to the general population (ExAC). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000710799 SCV002562510 pathogenic not provided 2022-02-09 criteria provided, single submitter clinical testing Affects a glycine residue in a Gly-X-Y motif in the triple helical region of the COL4A1 gene, where the majority of pathogenic missense variants occur, and is predicted to disrupt normal protein folding and function (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); 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: 34114234, 20733150, 20385946, 30653986, 19477666)
OMIM RCV002247544 SCV000196039 pathogenic Brain small vessel disease 1 with or without ocular anomalies 2012-06-01 no assertion criteria 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.