ClinVar Miner

Submissions for variant NM_144991.3(TSPEAR):c.364C>T (p.Arg122Trp)

gnomAD frequency: 0.00067  dbSNP: rs146257403
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Total submissions: 4
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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 RCV000218026 SCV000272572 uncertain significance not specified 2015-05-27 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Arg122Trp var iant in TSPEAR has not been previously reported in individuals with hearing loss . This variant has been identified in 0.15% (14/9534) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs 146257403). Computational prediction tools and conservation analyses do not pro vide strong support for or against an impact to the protein In summary, while th e clinical significance of the p.Arg122Trp variant is uncertain, the frequency d ata suggests that it is more likely to be benign.
Knight Diagnostic Laboratories, Oregon Health and Sciences University RCV001270088 SCV001448900 uncertain significance Autosomal recessive nonsyndromic hearing loss 98 2019-07-08 criteria provided, single submitter clinical testing
GeneDx RCV001569443 SCV001793518 likely benign not provided 2020-08-26 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001569443 SCV002200103 uncertain significance not provided 2022-10-03 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 122 of the TSPEAR protein (p.Arg122Trp). This variant is present in population databases (rs146257403, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with TSPEAR-related conditions. ClinVar contains an entry for this variant (Variation ID: 229377). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TSPEAR protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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