Submissions for variant NM_000545.8(HNF1A):c.1193_1195delinsGGT (p.Gln398_Gln399delinsArgTer)

dbSNP: rs1593060966

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001008744	SCV001168525	likely pathogenic	not provided	2019-02-18	criteria provided, single submitter	clinical testing	The c.1193_1195delAGCinsGGT variant in the HNF1A gene changes the Glutamine at position 398 to an Arginine residue and creates a premature Stop codon at position 399, denoted p.Gln398_Gln399delinsArgX. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1193_1195delAGCinsGGT variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016). In summary, we interpret this variant as likely pathogenic.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002319612	SCV002604911	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 rs1593060966 with MODY3.