Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV002470433 | SCV002767871 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 9 | 2019-08-28 | criteria provided, single submitter | clinical testing | A heterozygous missense variant, NM_194248.2(OTOF):c.1126G>A, has been identified in exon 12 of 47 of the OTOF gene. The variant is predicted to result in a minor amino acid change from aspartic acid to asparagine at position 376 of the protein (NP_919224.1(OTOF):p.(Asp376Asn)). The aspartic acid residue at this position has very high conservation (100 vertebrates, UCSC), and is located within the FerI functional domain. In silico predictions of pathogenicity for this variant are conflicting (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the database at a frequency of 0.0016% (4 heterozygotes, 0 homozygotes). The variant has been previously described as a VUS (Deafnessvariationdatabase). Based on the information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS). |