ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.1614+1G>C (rs111033312)

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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 RCV000155956 SCV000205668 pathogenic Rare genetic deafness 2013-09-09 criteria provided, single submitter clinical testing The c.1614+1G>C variant in SLC26A4 has been reported in the compound heterozygou s state with another SLC26A4 variant in one individual with hearing loss (Chen 2 011). This variant occurs in the invariant region (+/- 1/2) of the splice conse nsus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. In summary, this variant meets our criteria to be classified as pathogenic for hearing loss in an autosomal recessive manner.
Invitae RCV001202917 SCV001374052 likely pathogenic not provided 2020-07-09 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 14 of the SLC26A4 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in combination with another SLC26A4 variant individuals affected with hearing loss or Pendred syndrome (PMID: 29048421, 11919333). ClinVar contains an entry for this variant (Variation ID: 179170). 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SLC26A4 are known to be pathogenic (PMID: 16283880, 25394566, 26252218, 26445815). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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