Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Molecular Genetics Laboratory; Baylor College of Medicine | RCV000119820 | SCV000154746 | probable-pathogenic | Autosomal recessive nonsyndromic hearing loss 9 | criteria provided, single submitter | not provided | Converted during submission to Likely pathogenic. | |
| Fulgent Genetics, |
RCV000119820 | SCV002784070 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 9 | 2021-08-10 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003230408 | SCV003928737 | likely pathogenic | Nonsyndromic genetic hearing loss | 2023-04-06 | criteria provided, single submitter | clinical testing | Variant summary: OTOF c.1172delA (p.Lys391ArgfsX31) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 250524 control chromosomes (gnomAD). c.1172delA has been reported in the literature in an individual affected with auditory neuropathy (example: Tang_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Nonsyndromic Hearing Loss And Deafness, Type 9. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Invitae | RCV003556167 | SCV004292101 | pathogenic | not provided | 2023-08-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 133309). This premature translational stop signal has been observed in individual(s) with auditory neuropathy (PMID: 25991456). This variant is present in population databases (rs483353050, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Lys391Argfs*31) in the OTOF gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OTOF are known to be pathogenic (PMID: 18381613, 19250381, 22575033). |