ClinVar Miner

Submissions for variant NM_153676.4(USH1C):c.497-3C>A (rs958295779)

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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, Partners HealthCare Personalized Medicine RCV000610316 SCV000712220 uncertain significance not specified 2016-06-02 criteria provided, single submitter clinical testing The c.497-3C>A variant in USH1C has not been previously reported in individuals with hearing loss or Usher syndrome. Data from large population studies are insu fficient to assess the frequency of this variant in the general population. This variant is located in the 3' splice region. Computational tools suggest a possi ble impact to splicing. However, this information is not predictive enough to de termine pathogenicity. In summary, the clinical significance of the c.497-3C>A v ariant is uncertain.
Invitae RCV001064690 SCV001229603 uncertain significance not provided 2020-02-22 criteria provided, single submitter clinical testing This sequence change falls in intron 5 of the USH1C gene. It does not directly change the encoded amino acid sequence of the USH1C protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with USH1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 505102). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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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