ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.1225C>T (p.Arg409Cys) (rs147952620)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000411132 SCV000486998 likely pathogenic Pendred syndrome 2016-09-22 criteria provided, single submitter clinical testing
Invitae RCV000811142 SCV000951393 pathogenic not provided 2019-07-10 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 409 of the SLC26A4 protein (p.Arg409Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs147952620, ExAC 0.01%). This variant has been reported in several individuals affected with non-syndromic enlargement of vestibular aqueduct and hearing loss (PMID: 18167283, 23185506, 25372295). ClinVar contains an entry for this variant (Variation ID: 371421). Experimental studies have shown that this missense change leads to decreased expression in the cell and retention in the intracellular region (PMID: 23185506). A different missense substitution at this codon (p.Arg408His) has been determined to be pathogenic (PMID: 9618166, 19786220, 24224479). This suggests that the arginine residue is critical for SLC26A4 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery,Institute of Otolaryngology, Chinese PLA General Hospital RCV000770861 SCV000902369 likely pathogenic Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 2019-02-26 no assertion criteria provided case-control

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