Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000220688 | SCV000271461 | pathogenic | Rare genetic deafness | 2016-01-03 | criteria provided, single submitter | clinical testing | The p.Arg1993X variant in TECTA has not been previously reported in individuals with hearing loss and has been identified in 2/11544 Latino chromosomes by the E xome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs76057 4657). Although this variant has been seen in the general population, its freque ncy is low enough to be consistent with a recessive carrier frequency. This nons ense variant leads to a premature termination codon at position 1993 which is pr edicted to lead to a truncated or absent protein. Loss of function of the TECTA gene is an established disease mechanism in autosomal recessive hearing loss. In addition, some variants that result in a truncated protein may have the potenti al to cause hearing loss inherited in an autosomal dominant pattern (Colin 2008, Hildebrand 2011). However, there is insufficient evidence to predict whether th e p.Arg1993X variant can also lead to dominantly inherited hearing loss. In summ ary, this variant meets our criteria to be classified as pathogenic for hearing loss in an autosomal recessive manner based on the predicted impact of the varia nt on the protein. |
Knight Diagnostic Laboratories, |
RCV001270081 | SCV001448871 | pathogenic | not provided | 2017-01-09 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001270081 | SCV001999734 | uncertain significance | not provided | 2021-10-07 | criteria provided, single submitter | clinical testing | Reported in a patient in published literature (Hou et al., 2020); however, clinical data is limited; Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 21520338, 18575463, 31589614, 31980526) |