ClinVar Miner

Submissions for variant NM_000545.8(HNF1A):c.52G>T (p.Glu18Ter)

dbSNP: rs1876084046
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001194005 SCV001363224 likely pathogenic Maturity onset diabetes mellitus in young 2019-11-06 criteria provided, single submitter clinical testing Variant summary: HNF1A c.52G>T (p.Glu18X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (c.511C>T, p.Arg171X; c.526C>T, p.Gln176X). The variant was absent in 248304 control chromosomes (gnomAD). To our knowledge, no occurrence of c.52G>T in individuals affected with Maturity Onset Diabetes of the Young 3 and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Geisinger Clinic, Geisinger Health System RCV002285453 SCV002562138 pathogenic Maturity-onset diabetes of the young type 3 2022-08-02 criteria provided, single submitter research PVS1, PM2
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV001194005 SCV002601659 pathogenic 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 rs1876084046 with MODY3.
Ambry Genetics RCV001194005 SCV002643089 pathogenic Maturity onset diabetes mellitus in young 2016-03-16 criteria provided, single submitter clinical testing The p.E18* pathogenic mutation (also known as c.52G>T), located in coding exon 1 of the HNF1A gene, results from a G to T substitution at nucleotide position 52. This changes the amino acid from a glutamic acid to a stop codon within coding exon 1. Since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
GeneDx RCV003324818 SCV004030816 likely pathogenic not provided 2023-02-22 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 36257325, 35673428, 35328643, 32395877, 31517624)

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