ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.365dup (p.Ile124fs) (rs786204730)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Hearing Loss Variant Curation Expert Panel RCV000169571 SCV000840531 pathogenic Pendred syndrome 2018-09-10 reviewed by expert panel curation The p.Ile124Tyrfs variant in SLC26A4 is predicted to cause a premature stop codon in biologically-relevant-exon 4/21 that leads to a truncated or absent protein in a gene in which loss-of-function is an established mechanism (PVS1). The allele frequency of the p.Ile124fs variant is in 0.003% (1/30782) of South Asian chromosomes by the Genome Aggregation Database (, which is a low enough frequency to award PM2 based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss (PM2). At least one patient with the variant displayed features of enlarged vestibular aqueduct and Mondini malformation which are consistent with Pendred syndrome (PP4; PMID:15679828). This variant has been detected in 2 patients with hearing loss in trans with suspected pathogenic variants (PM3_P, PMID:15679828). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Pendred syndrome based on the ACMG/AMP criteria applied: PVS1, PM2, PP4, PM3_P.
Counsyl RCV000169571 SCV000221071 likely pathogenic Pendred syndrome 2015-01-22 criteria provided, single submitter literature only
CeGaT Praxis fuer Humangenetik Tuebingen RCV000488403 SCV000575531 likely pathogenic not provided 2016-09-01 criteria provided, single submitter clinical testing
Invitae RCV000488403 SCV000947141 pathogenic not provided 2019-06-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ile124Tyrfs*58) in the SLC26A4 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs773738163, ExAC 0.006%). This variant has been observed in several individuals affected with enlarged vestibular aqueduct (PMID: 15679828, 24051746). ClinVar contains an entry for this variant (Variation ID: 189148). 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.
Natera, Inc. RCV000169571 SCV001455795 pathogenic Pendred syndrome 2020-09-16 no assertion criteria provided clinical testing

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