Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000030530 | SCV000053201 | 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, |
RCV000030530 | SCV000926130 | pathogenic | Renal cysts and diabetes syndrome | 2019-07-06 | criteria provided, single submitter | literature only | |
| Victorian Clinical Genetics Services, |
RCV000030530 | SCV002766951 | pathogenic | Renal cysts and diabetes syndrome | 2022-09-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. 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. There is significant interfamilial and intrafamilial variability of HNF1B -related nephropathy (PMID: 33305128). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. These variants have been reported many times as pathogenic (DECIPHER). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been reported as pathogenic, and observed in indidivuals with diabetes mellitus, noninsulin-dependent (MODY) or glomerulocystic kidney disease (ClinVar, PMID: 11085914, PMID: 30259503). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Fulgent Genetics, |
RCV002477029 | SCV002777640 | pathogenic | Renal cysts and diabetes syndrome; Type 2 diabetes mellitus; Nonpapillary renal cell carcinoma | 2021-12-03 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002513268 | SCV003443072 | pathogenic | not provided | 2021-12-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 36849). This variant is also known as P159fsdelT. This premature translational stop signal has been observed in individual(s) with clinical features of HNF1B-related conditions (PMID: 11085914, 24429398). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Met160*) in the HNF1B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HNF1B are known to be pathogenic (PMID: 9398836, 12148114, 15068978, 20378641). |