Monogenic hearing loss

Gene: TMTC2

I don't know

Comment on list classification: Changing rating from grey to amber. Two families reported. Same variant in each. Both northern european decent.

Created: 8 Sep 2020, 10:42 p.m. | Last Modified: 8 Sep 2020, 10:42 p.m.

Panel Version: 2.60

Comment on mode of inheritance: Changing to imprinted status unknown. In one family the trait had been passed through the maternal side for two generations, but more evidence needed before saying paternally imprinted.

Created: 8 Sep 2020, 10:41 p.m. | Last Modified: 8 Sep 2020, 10:41 p.m.

Panel Version: 2.58

Not associated with a phenotype in OMIM.

PMID: 29671961- Guillen‐Ahlers et al 2018 - report a mother and son with of Northern European descent (mother and son) with Sensorineural hearing loss were found by exome sequencing to share a variant (rs35725509, missense variant) in the TMTC2 gene. This variant showed a minor allele frequency below 1% in 2,203 individuals of European American (EA) ancestry (NHLBI GO Exome Sequencing Project. In two generations, the trait has been passed through the maternal side


PMID: 27311106 - Runge et al 2016 - report a large multigenerational Northern European family in which 9 family members had bilateral, symmetric, progressive Sensorineural hearing loss that reached severe to profound loss in childhood. Using exome sequencing and linkage and association analyses they identified a fully penetrant sequence variant (rs35725509) in the TMTC2 gene region. The variant segregates with SNHL in the family. However, the mutation is found in a relatively high percentage of individuals of Northern European descent in the 1000 Genomes and Exome Sequencing (http://evs.gs.washington.edu/EVS/) European call sets (1% and 0.8%, respectively).

Created: 8 Sep 2020, 10:36 p.m. | Last Modified: 8 Sep 2020, 10:40 p.m.

Panel Version: 2.57

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Sensorineural hearing loss

Publications

• 29671961
• 27311106

I don't know

Two unrelated families reported, no functional evidence.
Sources: Expert list

Created: 2 Jan 2020, 5:45 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)

Phenotypes
Deafness

Publications

• 29671961
• 27311106