Submissions for variant NM_000545.8(HNF1A):c.431T>C (p.Leu144Pro)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002332031	SCV002633240	uncertain significance	Maturity onset diabetes mellitus in young	2018-11-29	criteria provided, single submitter	clinical testing	The p.L144P variant (also known as c.431T>C), located in coding exon 2 of the HNF1A gene, results from a T to C substitution at nucleotide position 431. The leucine at codon 144 is replaced by proline, an amino acid with similar properties. This variant was identified in one maturity-onset diabetes of the young family; however, clinical details were limited (Colclough K et al. Hum. Mutat., 2013 May;34:669-85). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on available evidence to date, the clinical significance of this alteration remains unclear.
Human Genetics Section, Sidra Medicine	RCV003889111	SCV004708150	likely pathogenic	Maturity-onset diabetes of the young type 3	2024-02-28	criteria provided, single submitter	research	The missense variant is located in a mutational hot spot and/or critical and well-established functional domain. The gene has low rate of benign missense variants. The condition associated with this gene has incomplete penetrance. In silico tools support a deleterious effect on the gene. Same codon with a different amino acid change as a known pathogenic variant of the gene. We therefore classify this variant as likely pathogenic