Haematuria
Gene: COL4A3
This gene was part of an initial gene list collated by Elizabeth Watson, North Bristol NHS Trust, Febuary 2019 on behalf of the GMS Renal Specialist Test Group. Gene Symbol submitted: COL4A3; Suggested initial gene rating: Green; Evidence for inclusion: PMID: 30506145; 29987460; 24052634 , Many relevant publications in pubmed.; Evidence for exclusion: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none provided; Other comments: Does Ellen Thomas mean Glycine residues, rather than cystine residues in her PanelAPP comment?Created: 3 Feb 2019, 3:19 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Alport syndrome, autosomal dominant #104200; Alport syndrome, autosomal recessive #203780; Hematuria, benign familial #141200
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on mode of pathogenicity: LOF mutations in collagen genes may cause a less severe phenotype than missense variants affecting particular residues (usually Cysteine). A curated set of known pathogenic variants could be made for this gene.Created: 29 Jan 2016, 12:18 p.m.
Comment on mode of inheritance: Monoallelic status is also important for management so both should be reported.Created: 29 Jan 2016, 12:16 p.m.
Biallelic disease usually causes Alport syndrome (kidney failure and deafness often in adolescence/early adulthood). Monoallelic disease causes autosomal dominant thin glomerular basement membrane nephropathy.Created: 7 Oct 2015, 12:58 p.m.
Phenotypes
Alport syndrome; proteinuria; haematuria; FSGS
Publications
Evidence for digenic inheritance in Alport syndrome? See PMID: 25575550, COL4A3, COL4A4 and COL4A6 genes.Created: 28 Aug 2015, 7:32 a.m.
Phenotypes for gene: COL4A3 were changed from Alport syndrome, autosomal recessive, 203780; Hematuria, benign familial, 141200; Alport syndrome, autosomal dominant, 104200; Alport Syndrome; Hematuria, Benign Familial; Alport Syndrome, X-Linked; Alport Syndrome, Autosomal Recessive; Alport Syndrome, Autosomal Dominant; thin glomerular basement membrane nephropathy or Alport syndrome; Alport syndrome, autosomal dominant; Alport syndrome, autosomal recessive; Alport Syndrome; (originally on Alport syndrome gene panel) to Alport syndrome, autosomal dominant OMIM:104200; Alport syndrome, autosomal recessive OMIM:203780; Hematuria, benign familial OMIM:141200
Publications for gene: COL4A3 were set to 17942953
Source NHS GMS was added to COL4A3. Rating Changed from Green List (high evidence) to Green List (high evidence)
This gene has been classified as Green List (High Evidence).
Publications for COL4A3 were set to 17942953
Mode of pathogenicity for COL4A3 was changed to Other - please provide details in the comments
Mode of inheritance for COL4A3 was changed to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Model of inheritance for gene COL4A3 was set to BIALLELIC, autosomal or pseudoautosomal
COL4A3 was added to Familial haematuriapanel. Source: Eligibility statement prior genetic testing
Model of inheritance for gene COL4A3 was set to BIALLELIC, autosomal or pseudoautosomal
COL4A3 was added to Familial haematuriapanel. Source: UKGTN
Model of inheritance for gene COL4A3 was set to BIALLELIC, autosomal or pseudoautosomal
COL4A3 was added to Familial haematuriapanel. Source: Illumina TruGenome Clinical Sequencing Services
Model of inheritance for gene COL4A3 was set to BIALLELIC, autosomal or pseudoautosomal
COL4A3 was added to Familial haematuriapanel. Source: Radboud University Medical Center, Nijmegen
COL4A3 was added to Familial haematuriapanel. Source: Eligibility statement prior genetic testing
COL4A3 was added to Familial haematuriapanel. Source: UKGTN
COL4A3 was added to Familial haematuriapanel. Source: Illumina TruGenome Clinical Sequencing Services
COL4A3 was added to Familial haematuriapanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,UKGTN,Eligibility statement prior genetic testing