ClinVar Miner

Submissions for variant NM_000545.8(HNF1A):c.1537A>T (p.Thr513Ser)

gnomAD frequency: 0.00001  dbSNP: rs753702603
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV001248990 SCV001422834 uncertain significance Maturity-onset diabetes of the young type 3 2020-01-22 criteria provided, single submitter curation The p.Thr513Ser variant in HNF1A has been reported in 1 European individual with MODY (PMID: 18003757), and has been identified in 0.002% (2/113456) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs753702603). 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, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2 (Richards 2015).
Labcorp Genetics (formerly Invitae), Labcorp RCV001879747 SCV002151364 uncertain significance not provided 2021-04-22 criteria provided, single submitter clinical testing This sequence change replaces threonine with serine at codon 513 of the HNF1A protein (p.Thr513Ser). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and serine. This variant is present in population databases (rs753702603, ExAC 0.003%). This variant has been observed in individual(s) with clinical features of MODY, type III (PMID: 18003757, 25555642). ClinVar contains an entry for this variant (Variation ID: 972779). 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 HNF1A 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 RCV005012689 SCV005634509 uncertain significance Diabetes mellitus type 1; Type 1 diabetes mellitus 20; Maturity-onset diabetes of the young type 3; Type 2 diabetes mellitus; Hepatic adenomas, familial; Nonpapillary renal cell carcinoma 2024-06-07 criteria provided, single submitter clinical testing

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