Newborns main panel

Gene: AVP

Special Consideration: Multiple MOIs for the same phenotype included.

Additional Information: AD (DN) and AR (LOF) forms of Diabetes insipidus, neurohypophyseal are included.

Created: 8 Jan 2026, 10:56 a.m. | Last Modified: 8 Jan 2026, 10:56 a.m.

Panel Version: 0.502

The mutant protein has a dominant negative effect but rare deletions, splicing and nonsense variants have been reported in ClinVar, LOVD and literature (PMID: 21498630;22168581;25740874). Therefore, the LOF algorithm remains switched on for this gene to allow detection of these variants.

Created: 12 Jun 2025, 10:58 a.m. | Last Modified: 12 Jun 2025, 10:59 a.m.

Panel Version: 0.480

Following consultation with the nephrology specialist group, it was raised that dominant variants in the AVP gene, associated with neurohypophyseal diabetes insipidus, act via a dominant negative effect rather than loss-of-function.

Variants result in misfolding and aggregation of the protein in the ER. AVP mutants complex with wild-type AVP to form heterodimers which are retained in the ER of secreting neurons, which leads to defective intracellular trafficking of wild-type AVP protein and a decrease in cell viability (PMID: 28920918; 31238300; 21498630; 22168581)

Created: 7 Apr 2025, 1:05 p.m. | Last Modified: 7 Apr 2025, 1:05 p.m.

Panel Version: 0.480

Publications

• 28920918
• 31238300
• 21498630
• 22168581

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

The mechanism of pathogenicity is loss-of-function (LOF).

Created: 1 Jun 2023, 2:40 p.m. | Last Modified: 1 Jun 2023, 2:40 p.m.

Panel Version: 0.137

PMID: 31238300 and PMID: 32052034

Created: 1 Jun 2023, 12:22 p.m. | Last Modified: 1 Jun 2023, 12:22 p.m.

Panel Version: 0.134