ClinVar Miner

Submissions for variant NM_000545.8(HNF1A):c.923C>T (p.Pro308Leu)

gnomAD frequency: 0.00002  dbSNP: rs754306821
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000455518 SCV000539305 uncertain significance not specified 2016-10-13 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Variant seen in 1 affected patient in HGMD. Max MAF of 0.03% in ExAC.
Labcorp Genetics (formerly Invitae), Labcorp RCV001861659 SCV002143545 uncertain significance not provided 2021-09-15 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with clinical features of autosomal dominant maturity-onset diabetes of the young (PMID: 18003757). This sequence change replaces proline with leucine at codon 308 of the HNF1A protein (p.Pro308Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs754306821, ExAC 0.03%). ClinVar contains an entry for this variant (Variation ID: 402948). 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 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.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002319499 SCV002604893 uncertain risk allele Maturity onset diabetes mellitus in young criteria provided, single submitter research Mutations in HNF1A gene can predispose to MODY3. It is associated with both micro and macrovascular complications of diabetes, especially cardiovascular complications. Associated with glucosuria. May respond well to sulfonylureas. However, more evidence is required to confer the association of this particular variant rs754306821 with MODY3.
Fulgent Genetics, Fulgent Genetics RCV002480333 SCV002785027 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 2021-11-29 criteria provided, single submitter clinical testing
Genetics Department, Catlab RCV004797811 SCV005419260 uncertain significance Maturity-onset diabetes of the young type 3 2024-10-15 criteria provided, single submitter clinical testing The c.923C>T variant in the HNF1A gene has not been previously described in patients with diabetes MODY to our knowledge. The variants has a very low frequency in gnomAD 4.0 (AF=1.0664e-05) (PM2) and REVEL value is 0.687 (PP3). With all the available evidence, the variant is classified as of unknown significance.

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