ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.164+1del (rs786204504)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169187 SCV000220430 likely pathogenic Pendred syndrome 2014-06-19 criteria provided, single submitter literature only
Invitae RCV001040907 SCV001204498 pathogenic not provided 2019-05-29 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 2 of the SLC26A4 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. Disruption of this splice site has been observed in combination with another SLC26A4 variant in individual(s) with clinical features of Pendred syndrome (PMID: 22717225, 27861301, 25724631). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 188838). 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). For these reasons, this variant has been classified as Pathogenic.

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