ClinVar Miner

Submissions for variant NM_000545.8(HNF1A):c.1274C>T (p.Thr425Met)

gnomAD frequency: 0.00002  dbSNP: rs1401743626
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine RCV001258181 SCV001435070 uncertain significance Maturity-onset diabetes of the young type 3 criteria provided, single submitter clinical testing
Baylor Genetics RCV001293985 SCV001482726 uncertain significance Type 1 diabetes mellitus 20 2019-02-21 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002319687 SCV002604913 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 rs1401743626 with MODY3.
Labcorp Genetics (formerly Invitae), Labcorp RCV002570633 SCV003006114 uncertain significance not provided 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 425 of the HNF1A protein (p.Thr425Met). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with HNF1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 979117). 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 with a positive predictive value of 95%. 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.

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