Tubulointerstitial kidney diseaseGene: MUC1
Comment on list classification: Rated as green due to numerous reports of variants within VNTR associated with mutant protein and single report of 2bp deletion outside VNTR with equivalent effect on protein. Note: variants within VNTR are unlikely to be detected by NGS.
Created: 27 Mar 2019, 12:36 p.m.
Comment on publications: Added PMID: 23946964 Bleyer and Kmoch, last updated 2016. Gene reviews entry on Autosomal Dominant Tubulointerstitial Kidney Disease, MUC1-Related
Created: 16 Jul 2019, 9:10 a.m. | Last Modified: 16 Jul 2019, 9:10 a.m.
Panel Version: 0.14
Comment on publications: Added PMID: 29520014 Wenzel et al 2018 which describes long read single molecule real time sequencing (SMRT) targeted to the MUC1-VNTR as an alternative strategy to the snapshot assay.
Created: 16 Jul 2019, 9:07 a.m. | Last Modified: 16 Jul 2019, 9:07 a.m.
Panel Version: 0.13
Comment on list classification: Changing the rating from Green to Amber as only 1 mutation has been found outside of the VNTR region. SNVs within the VNTR are unlikely to be detected by NGS.
Created: 12 Feb 2019, 4:03 p.m.
PMID: 29156055 (Yamamoto et al 2017) report a 2-bp deletion in MUC1 in a family with autosomal dominant tubulointerstitial kidney disease. It was found by exome sequencing and is located before the VNTR. The resulting mutant MUC1 protein had a very similar amino acid sequence and predicted 3D structure to the previously reported mutant protein
Created: 12 Feb 2019, 4:01 p.m.
PMID: 29967284 (Živná et al 2018) - developed immunohistochemical methods to detect the MUC1fs created by the cytosine duplication and, possibly, by other similar frameshift mutations. Found six families with five novel MUC1 frameshift mutations within the VNTR units that all predict production of the identical MUC1fs protein that is found in patients with the 27dupC duplication. They report that there are now 57 reported families with MUC1 mutations and 134 other families that they have identified (A.J. Bleyer, S. Kmoch, unpublished data). Of these 191 families, 183 have the 27dupC mutation and seven have a different mutation. All 191 affected families produce the same frameshifted protein.
Created: 12 Feb 2019, 3:02 p.m.
PMID: 23396133 (Kirby et al 2013) describe 6 families with an insertion of a single C in one copy (but a different copy in each family) of the repeat unit comprising the extremely long (~1.5-5 kb), GC-rich (>80%), coding VNTR in the mucin 1 gene. The insertion results in a frameshift which is predicted to produce a mutant protein that contains many copies of a novel repeat sequence but which lacks, owing to a novel stop codon shortly beyond the VNTR terminus, the downstream SEA self-cleavage module and both transmembrane and intracellular domains characteristic of the normal MUC1 precursor protein.
Created: 12 Feb 2019, 2:36 p.m.
This gene was part of an initial gene list collated by Emma Ashton (NE Thames Regional Genetics laboratory, GOSH NHS Foundation Trust) January 2019 on behalf of the GMS Renal Specialist Test Group.Gene Symbol submitted:MUC1;Suggested initial gene rating: Green;Evidence for inclusion: none provided;Evidence for exclusion: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): Common mutation is Nt.59dupC in 60-mer repeat unit unlikely to be detectable by NGS (VNTR 20-125 repeats), specific assay required
Created: 2 Feb 2019, 12:48 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Medullary cystic kidney disease 1 MIM 174000
Mode of pathogenicity
Other - please provide details in the comments
Publications for gene: MUC1 were set to 23396133; 29967284; 29156055; 29520014
Publications for gene: MUC1 were set to 23396133; 29967284; 29156055
Gene: muc1 has been classified as Green List (High Evidence).
Gene: muc1 has been classified as Amber List (Moderate Evidence).
Publications for gene: MUC1 were set to 23396133
gene: MUC1 was added gene: MUC1 was added to Tubulointerstitial kidney disease. Sources: Expert Review Green,NHS GMS Mode of inheritance for gene: MUC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MUC1 were set to 23396133 Phenotypes for gene: MUC1 were set to Medullary cystic kidney disease 1 MIM 174000 Mode of pathogenicity for gene: MUC1 was set to Other - please provide details in the comments