ClinVar Miner

Submissions for variant NM_000458.4(HNF1B):c.1657C>A (p.Pro553Thr)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000594491 SCV000705479 uncertain significance not provided 2018-05-17 criteria provided, single submitter clinical testing
Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg RCV000787052 SCV000925979 uncertain significance Renal cysts and diabetes syndrome 2019-07-06 criteria provided, single submitter literature only
Invitae RCV000594491 SCV002218786 uncertain significance not provided 2022-10-31 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 553 of the HNF1B protein (p.Pro553Thr). This variant is present in population databases (rs147798914, gnomAD 0.03%). This missense change has been observed in individual(s) with HNF1B-related conditions (PMID: 28420700). ClinVar contains an entry for this variant (Variation ID: 499802). 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 not expected to disrupt HNF1B protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV002497268 SCV002782714 uncertain significance Renal cysts and diabetes syndrome; Type 2 diabetes mellitus; Nonpapillary renal cell carcinoma 2022-03-30 criteria provided, single submitter clinical testing
GeneDx RCV000594491 SCV003853081 uncertain significance not provided 2022-09-28 criteria provided, single submitter clinical testing Reported in a patient with diabetes in published literature (Dubois-Laforgue et al., 2017); clinical information was not provided; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28420700)
PreventionGenetics, part of Exact Sciences RCV003403395 SCV004105687 uncertain significance HNF1B-related condition 2024-01-03 criteria provided, single submitter clinical testing The HNF1B c.1657C>A variant is predicted to result in the amino acid substitution p.Pro553Thr. This variant was reported in an individual with diabetes, but the clinical significance was uncertain (Table S1, Dubois-Laforgue et al. 2017. PubMed ID: 28420700). This variant is reported in 0.032% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-36047392-G-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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