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Limb disorders v7.12 NTN1 Eleanor Williams Phenotypes for gene: NTN1 were changed from to polydactyly, MONDO:0021003
Limb disorders v7.11 NTN1 Eleanor Williams Classified gene: NTN1 as Red List (low evidence)
Limb disorders v7.11 NTN1 Eleanor Williams Gene: ntn1 has been classified as Red List (Low Evidence).
Limb disorders v7.10 NTN1 Ida Ertmanska edited their review of gene: NTN1: Added comment: Comment on list classification: There is one patient reported in literature with a limb disorder (right hand polydactyly), heterozygous for a C-terminus missense variant in NTN1. At least 3 other patients, heterozygous for C-terminus NTN1 variants, had no polydcatyly. Based on the available evidence, NTN1 should be rated Red for Limb disorders.; Changed phenotypes to: polydactyly, MONDO:0021003
Limb disorders v7.10 NTN1 Ida Ertmanska gene: NTN1 was added
gene: NTN1 was added to Limb disorders. Sources: Literature
Mode of inheritance for gene: NTN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NTN1 were set to 28945198; 39648562
Review for gene: NTN1 was set to RED
Added comment: PMID: 39648562 (Toms et al., 2024) reports a patient with right hand polydactyly, heterozygous for a de novo variant in NTN1: NM_004822.3:c.1483T>A p.(Tyr495Asn). Sequencing method: WGS.The patient (Female, 30 years old, White British) also had chorioretinal coloboma and microphthalmia, and bilateral sensorineural hearing loss. The C-terminus variant is not found in gnomAD v4.1.0; in silico prediction tools: Revel score = 0.5 (Uncertain), AlphaMissense score = 0.806 (Deleterious Supporting); predicted NMD escape (https://www.deciphergenomics.org/gene/NTN1/overview/protein-genomic-info)

Confoundingly, patients with congenital mirror movements from 3 families reported in PMID: 28945198 (Meneret et al., 2017) who also harboured heterozygous NTN1 variants at the C-terminal end (p.Cys601Arg, p.Ile518del, p.Cys601Ser) had normal eyesight, no oculomotor abnormalities, and no hearing impairment.

This gene appears to be intolerant to LoF variants (NTN1 pLI score = 1). NTN1 is associated with Mirror movements 4, OMIM:618264 (OMIM entry accessed 10th Sep 2025).

Based on the available evidence, this gene can only be rated Red for Limb disorders.
Sources: Literature