Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001008481 | SCV001168252 | likely pathogenic | not provided | 2018-12-28 | criteria provided, single submitter | clinical testing | The c.5800dupC likely pathogenic variant in the OTOF gene has been reported previously in association with hearing loss (Rodriguez-Ballesteros et al., 2008; Mahdieh et al., 2012). The duplication causes a frameshift starting with codon Leucine 1934, changes this amino acid to a Proline residue and creates a premature Stop codon at position 251 of the new reading frame, denoted p.Leu1934ProfsX251. The c.5800dupC variant is not observed in large population cohorts (Lek et al., 2016). This likely pathogenic variant is predicted to result in protein truncation, as the last 64 amino acids are lost and replaced with 250 incorrect amino acids (Stenson et al., 2014). In summary, we interpret this variant as likely pathogenic. |
Laboratory of Human Genetics, |
RCV001730493 | SCV001762959 | pathogenic | Bilateral sensorineural hearing impairment | criteria provided, single submitter | research | in compound heterozygosis with another frameshift variant, both likely pathogenic in patient with auditory neuropathy | |
Fulgent Genetics, |
RCV000056052 | SCV002808870 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 9 | 2021-10-08 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001008481 | SCV004292070 | pathogenic | not provided | 2023-08-25 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the OTOF protein in which other variant(s) (p.Arg1939Gln) have been determined to be pathogenic (PMID: 22575033, 34424407, 34536124). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 65812). This variant is also known as p.Leu1934ProfsX185. This frameshift has been observed in individual(s) with deafness (PMID: 18381613). This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the OTOF gene (p.Leu1934Profs*251). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 64 amino acid(s) of the OTOF protein and extend the protein by 186 additional amino acid residues. |
Gene |
RCV000056052 | SCV000087112 | not provided | Autosomal recessive nonsyndromic hearing loss 9 | no assertion provided | literature only |