Monogenic diabetes
Region: ISCA-37432-Loss17q12 recurrent (RCAD syndrome) region (includes HNF1B) Loss
GRCh38 Position: 36458167-37854616
Haploinsufficiency Score: Sufficient evidence suggesting dosage sensitivity is associated with clinical phenotype
Triplosensitivity Score:
Required percent of overlap: 60%
Variant types: CNV Loss
3 reviews
Ida Ertmanska (Genomics England Curator)
Comment on list classification: 17q12 deletions affecting the gene HNF1B are a well established cause of Renal cysts and diabetes syndrome. Diabetes is often a presenting symptom in affected individuals. ClinGen Haploinsufficiency score is 3, suggesting dosage sensitivity. Hence, region ISCA-37432-Loss should be promoted to Green on Monogenic diabetes. The change is also tagged for expert review, in order to determine if there are any technical limitations that would prevent 17q12 deletions from being detected in this test.Created: 21 Apr 2026, 1:22 p.m. | Last Modified: 21 Apr 2026, 1:22 p.m.
Panel Version: 3.18
PMID: 41809577 Craven et al., 2025
11 paediatric patients with HNF1B variants, 7 presented with diabetes and 2 others developed diabetes later on. 6/11 patients had chronic kidney disease; 6 patients had evidence of hyperparathyroidism. 6/11 individuals had a 17q12 deletion, and 5/11 had heterozygous mutations in HNF1B.
PMID: 28420700 Dubois-Laforgu et al., 2017
Large cohort with HNF1B mutations (n = 101) or deletion (n = 100). Diabetes was present in 159 patients. At diagnosis, clinical symptoms of diabetes were present in 67 of 144 patients and HNF1B renal disease in 64 of 102.Created: 21 Apr 2026, 1:14 p.m. | Last Modified: 21 Apr 2026, 1:14 p.m.
Panel Version: 3.18
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Type 2 diabetes mellitus, OMIM:125853; Renal cysts and diabetes syndrome, OMIM:137920
Publications
Arina Puzriakova (Genomics England Curator)
The required percent of overlap for this region has been changed from 80% to 60% and the genomic location has been updated inline with ClinGen following NHS Genomic Medicine Service approval.Created: 16 Mar 2022, 1:08 p.m. | Last Modified: 16 Mar 2022, 1:08 p.m.
Panel Version: 2.47
Ivone Leong (Genomics England Curator)
Gene changed to grey status after consultation with Professor Sian Ellard (South West GLH) that this gene is not appropriate for the panel.Created: 25 Jan 2019, 11:57 a.m.
Details
- ISCA ID
- ISCA-37432-Loss
- ISCA Region Name
- 17q12 recurrent (RCAD syndrome) region (includes HNF1B) Loss
- Chromosome
- 17
- GRCh38 Coordinates
- 36458167-37854616
- Haploinsufficiency Score
- Sufficient evidence suggesting dosage sensitivity is associated with clinical phenotype
- Triplosensitivity Score
- Required percent of overlap
- 60%
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
- Sources
-
- Expert Review Amber
- Phenotypes
-
- 614527
- utero-vaginal atresia
- RCAD syndrome
- Schizophrenia
- Chromosome 17q12 deletion syndrome
- delayed development, intellectual disability
- global developmental delay
- Autism Spectrum Disorder
- Renal cysts and diabetes syndrome
- Mayer-Rokitansky-Kster-Hauser (MRKH) syndrome in females
- Tags
- Clinvar variants
- Variants in
- Penetrance
- None
- Variant types
- CNV Loss
History Filter Activity
Added Tag, Added Tag
Ida Ertmanska (Genomics England Curator)Tag Q2_26_promote_green tag was added to Region: ISCA-37432-Loss. Tag Q2_26_expert_review tag was added to Region: ISCA-37432-Loss.
Entity classified by Genomics England curator
Ida Ertmanska (Genomics England Curator)Region: isca-37432-loss has been classified as Amber List (Moderate Evidence).
Removed Tag
Ida Ertmanska (Genomics England Curator)Tag curated_removed was removed from Region: ISCA-37432-Loss.
Changed GRCh38, Changed Required Overlap Percentage
Arina Puzriakova (Genomics England Curator)GRCh38 position for ISCA-37432-Loss was changed from 36458167-37854617 to 36458167-37854616. Required Overlap Percentage for ISCA-37432-Loss was changed from 80 to 60.
Added Tag
Arina Puzriakova (Genomics England Curator)Tag curated_removed tag was added to Region: ISCA-37432-Loss.
Panel promoted to version 1.0
Ivone Leong (Genomics England Curator)Ivone Leong: Gene changed to grey status af
Entity classified by Genomics England curator
Ivone Leong (Genomics England Curator)Region: isca-37432-loss has been removed from the panel.
Created, Added New Source, Set mode of inheritance, Set Phenotypes
Ellen McDonagh (Genomics England Curator)Region: ISCA-37432-Loss was added Region: ISCA-37432-Loss was added to Monogenic diabetes. Sources: Expert Review Green Mode of inheritance for Region: ISCA-37432-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for Region: ISCA-37432-Loss were set to 614527; utero-vaginal atresia; RCAD syndrome; Schizophrenia; Chromosome 17q12 deletion syndrome; delayed development, intellectual disability; global developmental delay; Autism Spectrum Disorder; Renal cysts and diabetes syndrome; Mayer-Rokitansky-Kster-Hauser (MRKH) syndrome in females