Hearing lossGene: TMTC2
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
Sensorineural hearing loss
Gene: tmtc2 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: TMTC2 were changed from Deafness to Deafness; Sensorineural hearing loss
Mode of inheritance for gene: TMTC2 was changed from MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
gene: TMTC2 was added gene: TMTC2 was added to Hearing loss. Sources: Expert list Mode of inheritance for gene: TMTC2 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) Publications for gene: TMTC2 were set to 29671961; 27311106 Phenotypes for gene: TMTC2 were set to Deafness Review for gene: TMTC2 was set to AMBER