ClinVar Miner

Submissions for variant NM_144672.4(OTOA):c.1807G>T (p.Val603Phe)

gnomAD frequency: 0.00004  dbSNP: rs775686301
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Total submissions: 2
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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 RCV000223640 SCV000272227 uncertain significance not specified 2015-02-05 criteria provided, single submitter clinical testing The p.Val603Phe variant in OTOA has not been previously reported in individuals with hearing loss and or in large population studies. Computational prediction t ools and conservation analyses do not provide strong support for or against an i mpact to the protein. This variant is located in the first base of the exon, whi ch is part of the 3? splice region. Computational tools do not suggest an impact to splicing. However, this information is not predictive enough to rule out pat hogenicity. In summary, the clinical significance of the p.Val603Phe variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV001857747 SCV002204409 pathogenic not provided 2023-11-20 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 603 of the OTOA protein (p.Val603Phe). This variant is present in population databases (no rsID available, gnomAD 0.007%). This missense change has been observed in individual(s) with nonsyndromic deafness (PMID: 26029705, 26969326; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is also known as c.1570G>T (p.Val524Phe). ClinVar contains an entry for this variant (Variation ID: 229067). 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. For these reasons, this variant has been classified as Pathogenic.

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