ClinVar Miner

Submissions for variant NM_001256317.3(TMPRSS3):c.999del (p.Asp334fs)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003041396 SCV003444391 pathogenic not provided 2024-02-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asp334Metfs*24) in the TMPRSS3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TMPRSS3 are known to be pathogenic (PMID: 16021470, 26969326). This variant is present in population databases (rs748150602, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with sensorineural deafness (PMID: 28566687). ClinVar contains an entry for this variant (Variation ID: 2138389). For these reasons, this variant has been classified as Pathogenic.
King Laboratory, University of Washington RCV003155505 SCV003844183 pathogenic Autosomal recessive nonsyndromic hearing loss 8 2023-02-28 criteria provided, single submitter research This variant occurred in compound heterozygosity with a TMPRSS3 frameshift variant in two siblings with bilateral sensorineural hearing loss of onset <18 years, in a study of pediatric hearing loss conducted by the King Laboratory (Carlson RJ et al. JAMA-OtoHNS 2023). These siblings’ have a maternal half-aunt with childhood-onset hearing loss, and the family has no other history of hearing loss. This variant is a single base pair deletion that leads to a frameshift which is predicted to lead to the addition of 23 incorrect amino acids resulting in a premature stop at codon 357 of the 454-amino acid TMPRSS3 protein. As of January 2023, this variant has not been reported to ClinVar and is not found on gnomAD. Based on the prediction that the variant leads to protein truncation, compound heterozygosity with a loss-of-function variant, co-segregation with the phenotype in the family, and goodness of fit of genotype to phenotype, we conclude that this variant is pathogenic.
Fulgent Genetics, Fulgent Genetics RCV003155505 SCV005664115 likely pathogenic Autosomal recessive nonsyndromic hearing loss 8 2024-06-08 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.