Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000030527 | SCV000053198 | likely pathogenic | Renal cysts and diabetes syndrome | 2011-08-18 | criteria provided, single submitter | curation | Converted during submission to Likely pathogenic. |
| Institute of Human Genetics, |
RCV000030527 | SCV000926159 | likely pathogenic | Renal cysts and diabetes syndrome | 2019-07-06 | criteria provided, single submitter | literature only | |
| Clinical Genomics, |
RCV002464085 | SCV002605445 | likely pathogenic | Maturity onset diabetes mellitus in young | criteria provided, single submitter | research | HNF1B gene mutations are associated with early onset diabetes and pancreatic atrophy. It is also associated with multiple renal manifestations including renal cysts, Tubulointerstitial disease, glomerulocystic disease, renal hypoplasia, hypomagnesemia.However no sufficient evidence is found to ascertain the role of this particular variant rs193922487, yet. | |
| Victorian Clinical Genetics Services, |
RCV000030527 | SCV002768333 | uncertain significance | Renal cysts and diabetes syndrome | 2022-02-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0103 - Dominant negative, loss of function, and gain of function are all reported mechanisms of disease in this gene and are associated with type 2 diabetes mellitus (MIM#125853) and renal cysts and diabetes syndrome (MIM#137920; OMIM, PMID: 25536396, 11845238, 15509593). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Variable types and ages of onset of renal disease have been associated with HNF1B variants (PMID: 2976441). (I) 0200 - Variant is predicted to result in a missense amino acid change from serine to asparagine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0503 - Missense variant consistently predicted to be tolerated by multiple in silico tools or not conserved in placental mammals with a minor amino acid change. (SB) 0506 - Abnormal splicing is not predicted and nucleotide is poorly conserved. This variant is in the last coding base of exon 1 and is therefore in a splice region. (SB) 0600 - Variant is located in the annotated hepatocyte nuclear factor 1 N-terminus domain (DECIPHER). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0803 - This variant has limited previous evidence of pathogenicity in an unrelated individual observed by a clinical laboratory in ClinVar. (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |