Submissions for variant NM_000545.8(HNF1A):c.1417C>T (p.Gln473Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003557796	SCV004295436	pathogenic	not provided	2024-06-12	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln473*) in the HNF1A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HNF1A are known to be pathogenic (PMID: 15928245, 18003757). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with maturity onset diabetes of the young (PMID: 21224407). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004783079	SCV005395005	pathogenic	Maturity onset diabetes mellitus in young	2024-09-10	criteria provided, single submitter	clinical testing	Variant summary: HNF1A c.1417C>T (p.Gln473X) 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. The variant was absent in 249840 control chromosomes. c.1417C>T has been reported in the literature in individuals affected with Maturity Onset Diabetes Of The Young 3 (Awa_2011). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 21224407). ClinVar contains an entry for this variant (Variation ID: 2735987). Based on the evidence outlined above, the variant was classified as pathogenic.