Respiratory ciliopathies including non-CF bronchiectasis

Gene: TTC12

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 11 Dec 2025, 4:33 p.m. | Last Modified: 11 Dec 2025, 4:33 p.m.

Panel Version: 4.50

Green List (high evidence)

Comment on list classification: There is sufficient evidence available (10 unrelated cases) for the association of biallelic TTC12 patients with respiratory ciliopathy. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 4 Jul 2025, 11:12 a.m. | Last Modified: 4 Jul 2025, 11:12 a.m.

Panel Version: 4.8

The ClinGen Motile Ciliopathy expert panel has classified the association of TTC12 gene to ciliary dyskinesia, primary, 45 (MONDO:0032924) as 'Definitive'. More information can be found in https://search.clinicalgenome.org/CCID:008762.

PMID:36273201 - Five unrelated families with multisystem ciliopathy syndromes were studies, of which three were identified with biallelic variants in TTC12 gene. Two of them had respiratory phenotype.

PMID:37325566 - Three unrelated male patients from a large cohort of infertile Chinese males with asthenoteratozoospermia were identified with homozygous TTC12 variants. They also had a mild PCD-related nasosinusitis phenotype, which is a respiratory cilia impairment. However, they declined to undergo further investigation.

PMID:38992144 - A novel homozygous missense TTC12 variant was identified in an infertile Pakistani male with severe oligoasthenoteratozoospermia and primary ciliary dyskinesia. The patient also presented with sinusitis.

Created: 4 Jul 2025, 11:10 a.m. | Last Modified: 17 Jul 2025, 1:48 p.m.

Panel Version: 4.41

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ciliary dyskinesia, primary, 45, OMIM:618801

Publications

• 36273201
• 37325566
• 38992144

Submitted on behalf of NHS GMS "Only 6 variants in HGMD, all from the one study Thomas et al. Again as in NKE10 its not clear that full variant analysis has been done to ACGS standard, e.g. the homozygous variant c.1700T>G being described as pathogenic appear to be based on PM2 but has low frequency in gnomad and parents are related, PP3, PM1 (tricky to use in a new assocaited gene), and PS3 for study showing reduced TTC12. There is clearly strong evidence in this particular study but would argue that its too soon for inclusion in a diagnostic panel, but warrants further study. Amber genes can be included in panel designs for this research."

Created: 8 Mar 2022, 11:15 a.m. | Last Modified: 8 Mar 2022, 11:15 a.m.

Panel Version: 1.55

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed.

Created: 8 Mar 2022, 11:15 a.m. | Last Modified: 8 Mar 2022, 11:20 a.m.

Panel Version: 1.55

Comment on list classification: This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be promoted to Green at the next review.

Created: 2 Dec 2020, 2:42 p.m. | Last Modified: 2 Dec 2020, 2:42 p.m.

Panel Version: 1.36

Green List (high evidence)

Four unrelated families with LoF variants reported with a respiratory phenotype.
Sources: Expert list

Created: 25 May 2020, 7:35 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ciliary dyskinesia

Publications

• 31978331

Variants in this GENE are reported as part of current diagnostic practice