ClinVar Miner

Submissions for variant NM_000458.4(HNF1B):c.494G>A (p.Arg165His)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg RCV000013482 SCV000926123 likely pathogenic Renal cysts and diabetes syndrome 2019-07-06 criteria provided, single submitter literature only
Molecular Biology Laboratory, Fundació Puigvert RCV000013482 SCV001425087 likely pathogenic Renal cysts and diabetes syndrome 2020-02-01 criteria provided, single submitter research
Athena Diagnostics Inc RCV001659694 SCV001880034 pathogenic not provided 2020-12-16 criteria provided, single submitter clinical testing This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant appears to occur de novo in multiple individuals with clinical features associated with this gene. This variant has been identified in multiple unrelated individuals with clinical features associated with this gene. Assessment of experimental evidence suggests this variant results in abnormal protein function. This variant reduces the transactivation capacity of the protein (PMID: 15509593). Computational tools predict that this variant is damaging.
Genetic Services Laboratory, University of Chicago RCV001659694 SCV002069114 likely pathogenic not provided 2018-10-05 criteria provided, single submitter clinical testing
Invitae RCV001659694 SCV002245826 pathogenic not provided 2021-10-12 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt HNF1B protein function. ClinVar contains an entry for this variant (Variation ID: 12647). This missense change has been observed in individual(s) with renal cysts and diabetes syndrome (PMID: 15068978, 22051731, 24254850, 31198537). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with histidine at codon 165 of the HNF1B protein (p.Arg165His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine.
Molecular Genetics, Madras Diabetes Research Foundation RCV002051783 SCV002318388 likely pathogenic Maturity onset diabetes mellitus in young criteria provided, single submitter clinical testing
Genetics and Molecular Pathology, SA Pathology RCV002466400 SCV002761482 pathogenic Type 2 diabetes mellitus 2021-08-04 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002482860 SCV002802906 pathogenic Renal cysts and diabetes syndrome; Type 2 diabetes mellitus; Nonpapillary renal cell carcinoma 2021-11-17 criteria provided, single submitter clinical testing
OMIM RCV000013482 SCV000033729 pathogenic Renal cysts and diabetes syndrome 2005-03-01 no assertion criteria provided literature only
Yale Center for Mendelian Genomics, Yale University RCV000013482 SCV002106557 likely pathogenic Renal cysts and diabetes syndrome 2019-01-17 no assertion criteria provided literature only

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