ClinVar Miner

Submissions for variant NM_175914.5(HNF4A):c.1267C>T (p.Pro423Ser)

gnomAD frequency: 0.00002  dbSNP: rs1063239
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000117235 SCV000151408 uncertain significance not provided 2013-07-23 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002483195 SCV002792557 uncertain significance Maturity-onset diabetes of the young type 1; Type 2 diabetes mellitus; Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young 2021-09-14 criteria provided, single submitter clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV003148649 SCV003806252 uncertain significance Maturity onset diabetes mellitus in young criteria provided, single submitter research Potent mutations in HNF4A are associated with poor insulin secretion in response to hyperglycemia. Associated with MODY1. Patients initially respond well to sulfonylureas but eventually become insulin dependent. However, more evidence is required to ascertain the role of this particular variant rs1063239 in MODY, yet.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003323405 SCV004029948 uncertain significance not specified 2023-07-02 criteria provided, single submitter clinical testing Variant summary: HNF4A c.1267C>T (p.Pro423Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251382 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1267C>T has been reported in the literature in individuals affected with Diabetes (example, Aguilera_2004) and as "not possibly/putatively pathogenic" at-least one case in the Jackson Heart Study cohort, in which a majority (>80%) of variant carriers did not develop diabetes. These report(s) do not provide unequivocal conclusions about association of the variant with Maturity Onset Diabetes Of The Young 1/Neonatal Diabetes Mellitus. To our knowledge, no informative experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 15111529, 22308320, 24097065, 30648609). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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