Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute of Human Genetics, |
RCV000787100 | SCV000926029 | likely pathogenic | Renal cysts and diabetes syndrome | 2019-07-06 | criteria provided, single submitter | literature only | |
| Broad Center for Mendelian Genomics, |
RCV001254704 | SCV001430772 | uncertain significance | Congenital anomaly of kidney and urinary tract | 2020-05-28 | criteria provided, single submitter | research | The heterozygous p.Ser342Pro variant in HNF1B was identified by our study in 1 individual with congenital anomaly of kidney and urinary tract (CAKUT) as well as this individuals unaffected father (PMID: 24429398). It is of note that reduced penetrance has been previously described in CAKUT (PMID: 29293093). This variant has also been reported in ClinVar (Variation ID# 635613). This variant has been identified in 0.0009% (1/112178) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org). Please note that for diseases with clinical variability, or reduced penetrance, pathogenic variants may be present at a low frequency in the general population. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Ser342Pro variant is uncertain. ACMG/AMP Criteria applied: PM2_supporting (Richards 2015). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003994116 | SCV004813602 | uncertain significance | not specified | 2024-02-07 | criteria provided, single submitter | clinical testing | Variant summary: HNF1B c.1024T>C (p.Ser342Pro) results in a non-conservative amino acid change located in the Hepatocyte nuclear factor 1, beta isoform, C-terminal domain (IPR006897) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 248598 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1024T>C has been reported in the literature in at least one heterozygous individual affected with Congenital anomalies of the kidney and urinary tract (CAKUT) (e.g. Hwang_2014). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 24429398). ClinVar contains an entry for this variant (Variation ID: 635613). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Yale Center for Mendelian Genomics, |
RCV001254704 | SCV002106497 | likely pathogenic | Congenital anomaly of kidney and urinary tract | 2018-08-24 | no assertion criteria provided | literature only |