Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003230388 | SCV003928740 | uncertain significance | not specified | 2023-04-21 | criteria provided, single submitter | clinical testing | Variant summary: OTOF c.3413T>C (p.Leu1138Pro) results in a non-conservative amino acid change located in the C2 domain (IPR000008) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 241812 control chromosomes. c.3413T>C has been reported in the literature in at least two compound heterozygous individuals affected with Nonsyndromic Hearing Loss (e.g., Rodriguez-Ballesteros_2008). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Labcorp Genetics |
RCV003556144 | SCV004292085 | pathogenic | not provided | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1138 of the OTOF protein (p.Leu1138Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with deafness (PMID: 18381613). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 65799). 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 expected to disrupt OTOF protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV000056038 | SCV000087098 | not provided | Autosomal recessive nonsyndromic hearing loss 9 | no assertion provided | literature only |