ClinVar Miner

Submissions for variant NM_001378609.3(OTOGL):c.3434C>T (p.Ala1145Val)

gnomAD frequency: 0.00006  dbSNP: rs374368341
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000608017 SCV000711628 uncertain significance not specified 2017-03-07 criteria provided, single submitter clinical testing The p.Ala1136Val variant in OTOGL has been identified by our laboratory in 1 ind ividual with hearing loss, but the variant did not segregate with disease in an affected sibling. It has also been identified in 3/64954 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP r s374368341). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational predic tion tools and conservation analyses do not provide strong support for or agains t an impact to the protein. In summary, the clinical significance of the p.Ala11 36Val variant is uncertain.
Revvity Omics, Revvity RCV003133392 SCV003816551 uncertain significance Autosomal recessive nonsyndromic hearing loss 84B 2020-02-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV003343941 SCV004068438 uncertain significance Inborn genetic diseases 2023-08-02 criteria provided, single submitter clinical testing The c.3407C>T (p.A1136V) alteration is located in exon 29 (coding exon 29) of the OTOGL gene. This alteration results from a C to T substitution at nucleotide position 3407, causing the alanine (A) at amino acid position 1136 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV005091588 SCV005848013 uncertain significance not provided 2024-05-09 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1136 of the OTOGL protein (p.Ala1136Val). This variant is present in population databases (rs374368341, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with OTOGL-related conditions. ClinVar contains an entry for this variant (Variation ID: 504848). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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