Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000604852 | SCV000710845 | likely pathogenic | Rare genetic deafness | 2017-02-14 | criteria provided, single submitter | clinical testing | The p.Ile515Thr (NM_194248.2 c.1544T>C, ClinVar Variation ID#6143) variant in OT OF has been reported in 1 compound heterozygous individual with hearing loss who had a temperature-sensitive auditory neuropathy phenotype, in trans with a nons ense variant, and segregated with disease in an affected family member (Varga 20 06, Strenzke 2016, Avraham 2016). This variant has also been reported in 1 homoz ygous individual with hearing loss and in 3 affected homozygous family members, who all had a second missense OTOF variant of uncertain significance in cis (Mir ghomizadeh 2002). A knock-in mouse model homozygous for the p.Ile515Thr variant was shown to have hearing loss (Strenzke 2016). This variant has also been ident ified in 0.002% (1/65,772) of European chromosomes by the Exome Aggregation Cons ortium (ExAC, http://exac.broadinstitute.org; dbSNP rs80356586). Although this v ariant has been seen in the general population, its frequency is low enough to b e consistent with a recessive carrier frequency. In summary, although additional studies are required to fully establish its clinical significance, the p.Ile515 Thr variant is likely pathogenic for OTOF-related hearing loss in an autosomal r ecessive manner based upon biallelic observations in patients, low frequency in controls, and an animal model. |
OMIM | RCV000006517 | SCV000026700 | pathogenic | Auditory neuropathy, autosomal recessive, 1 | 2006-07-01 | no assertion criteria provided | literature only | |
Gene |
RCV000021035 | SCV000041689 | association | Deafness, autosomal recessive 9 | 2015-07-30 | no assertion criteria provided | literature only | |
OMIM | RCV000021035 | SCV000222658 | pathogenic | Deafness, autosomal recessive 9 | 2006-07-01 | no assertion criteria provided | literature only |