Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000211839 | SCV000206348 | pathogenic | Rare genetic deafness | 2014-06-10 | criteria provided, single submitter | clinical testing | The Gln994fs variant in OTOF has been reported in one Chinese individual with te mperature sensitive non-syndromic auditory neuropathy (Wang 2010) who was compou nd heterozygous with a second OTOF variant. The Gln994fs variant has not been id entified in large population studies. This variant is predicted to cause a frame shift, which alters the protein?s amino acid sequence beginning at position 994 and leads to a premature termination codon 7 amino acids downstream. This altera tion is then predicted to lead to a truncated or absent protein. In summary, thi s variant meets our criteria to be classified as pathogenic (www.partners.org/pe rsonalizedmedicine/lmm). |
Gene |
RCV002307412 | SCV002601528 | pathogenic | not provided | 2022-05-19 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 33426078, 20504331) |
Invitae | RCV002307412 | SCV004292090 | pathogenic | not provided | 2023-07-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln994Valfs*7) 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). This variant is present in population databases (rs727505157, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with temperature sensitive non-syndromic auditory neuropathy (PMID: 20504331). This variant is also known as c.2975_2978delAG (p.Q994VfsX6) . ClinVar contains an entry for this variant (Variation ID: 179828). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV000156627 | SCV000087094 | not provided | Autosomal recessive nonsyndromic hearing loss 9 | no assertion provided | literature only |