ClinVar Miner

Submissions for variant NM_144991.3(TSPEAR):c.802C>T (p.Arg268Ter)

gnomAD frequency: 0.00001  dbSNP: rs782471965
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000616190 SCV000712848 uncertain significance not specified 2017-01-17 criteria provided, single submitter clinical testing The p.Arg268X variant in TSPEAR has not been previously reported in individuals with hearing loss, but has been identified in 1/66396 of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP r s782471965). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. This nonsense varian t leads to a premature termination codon at position 268, which is predicted to lead to a truncated or absent protein. However, there is only moderate evidence to support an association of TSPEAR with autosomal recessive nonsyndromic hearin g loss. In summary, the clinical significance of the p.Arg268X variant is uncert ain.
Labcorp Genetics (formerly Invitae), Labcorp RCV003767454 SCV004624791 pathogenic not provided 2023-06-20 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 505557). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with TSPEAR-related conditions. This sequence change creates a premature translational stop signal (p.Arg268*) in the TSPEAR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TSPEAR are known to be pathogenic (PMID: 34042254). This variant is present in population databases (rs782471965, gnomAD 0.0009%).

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