Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000216138 | SCV000272237 | uncertain significance | not specified | 2018-05-18 | criteria provided, single submitter | clinical testing | The p.Lys1306Asn variant in OTOF has been previously identified by our laborator y in 1 individual with hearing loss, who also had a pathogenic variant in a diff erent gene that was sufficient to explain the hearing loss. This variant has bee n identified in 4/110706 of European chromosomes by the Genome Aggregation Datab ase (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs774929350), and has been reported in ClinVar (Variant ID:229077). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogeni c role. Computational prediction tools and conservation analysis suggest that th is variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the p.Lys1306Asn variant is uncertain. ACMG/AMP criteria applied: BP4, PM2_Supportin g. |
| Illumina Laboratory Services, |
RCV000338389 | SCV000429605 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 9 | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Baylor Genetics | RCV000338389 | SCV001524174 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 9 | 2020-06-08 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Prevention |
RCV003937853 | SCV004749614 | uncertain significance | OTOF-related condition | 2024-02-08 | criteria provided, single submitter | clinical testing | The OTOF c.3918G>C variant is predicted to result in the amino acid substitution p.Lys1306Asn. This variant has been observed in heterozygous state in patient with non-syndromic hearing loss (Table S2, Almontashiri et al. 2018. PMID: 29048421). Alternative variant at the same codon p.Lys1306Thr has been observed in compound heterozygous state in an individual with hearing loss, however this individual had also two compound heterozygous variant in gene CDH23 (Table 1, Adeyemo et al. 2022. PubMed ID: 34837038). This variant is reported in 0.0044% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |