ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.85G>C (p.Glu29Gln) (rs111033205)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000036509 SCV000060164 pathogenic Rare genetic deafness 2015-09-14 criteria provided, single submitter clinical testing The p.Glu29Gln variant in SLC26A4 has been identified in multiple individuals wi th hearing loss and temporal bone abnormalities including over 15 probands who w ere compound heterozygous with another pathogenic variant in SLC26A4, and it has segregated in three affected siblings (Albert 2006, Campbell 2001, Gardner 2006 , Ladsous 2014, Pera 2008, Pourova 2010, Rendtorff 2013, LMM unpublished data). Functional studies have demonstrated that this variant impacts the protein func tion (Pera 2008). In summary, this variant meets our criteria to be classified as pathogenic for DFNB4 nonsyndromic hearing loss or Pendred syndrome in an auto somal recessive manner.
Counsyl RCV000169251 SCV000220535 likely pathogenic Pendred syndrome 2014-07-23 criteria provided, single submitter literature only
Illumina Clinical Services Laboratory,Illumina RCV000778809 SCV000915189 pathogenic SLC26A4-Related Disorders 2018-11-24 criteria provided, single submitter clinical testing Across a selection of the available literature, the SLC26A4 c.85G>C (p.Glu29Gln) missense variant has been reported in at least nine studies in which it was identified in a total of 18 individuals, including in a compound heterozygous state in 14 individuals, in a heterozygous state in three individuals, in a double heterozygous state in one individual and in one individual with unknown zygosity. Affected individuals were diagnosed with either Pendred syndrome, an autosomal recessive form of deafness, or enlarged vestibular aqueduct or Mondini dysplasia (Campbell et al. 2001; Prasad et al. 2004; Blons et al. 2004; Alberts et al. 2006; Yang et al. 2007; Pera et al. 2008; Pourova et al. 2010; Rendtorff et al. 2013; Ladous et al. 2014). The p.Glu29Gln variant was found to segregate in at least one study (Yang et al. 2007). The variant was absent from 469 controls and is reported at a frequency of 0.000229 in the European (non-Finnish) population of the Genome Aggregation Database. Functional studies using fluorimetric measurements showed that the p.Glu29Gln variant protein has reduced chloride/iodide transport (Pera et al. 2008). Based on the collective evidence, the p.Glu29Gln variant is classified as pathogenic for SLC26A4-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
OMIM RCV000005111 SCV000025287 pathogenic Enlarged vestibular aqueduct 2008-08-01 no assertion criteria provided literature only
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000656195 SCV000678389 likely pathogenic Wolff-Parkinson-White pattern 2017-07-14 no assertion criteria provided research This variant was identified in an individual with Wolff-Parkinson-White syndrome
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery,Institute of Otolaryngology, Chinese PLA General Hospital RCV000005111 SCV000902384 likely pathogenic Enlarged vestibular aqueduct 2019-02-26 no assertion criteria provided case-control

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