ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.2162C>T (p.Thr721Met) (rs121908363)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000154350 SCV000204013 pathogenic Rare genetic deafness 2016-03-29 criteria provided, single submitter clinical testing The p.Thr721Met variant in SLC26A4 has been reported in at least 7 individuals f rom 5 families with hearing loss and enlarged vestibular aqueduct (EVA) or Pendr ed Syndrome (Chen 2011, Ishihara 2010, Kahrizi 2009, Lopez-Bigas 2001, Usami 199 9). Individuals were either homozygous (2 families) or heterozygous with anoth er pathogenic variant (3 families). Compound heterozygous variants were confir med to be in trans in at least one family. In addition, a study showed that the Thr721Met variant impacts protein function (Ishihara 2010). This variant has b een identified in 5/11486 Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs121908363); however, this freque ncy is low enough to be consistent with a recessive carrier frequency. In summa ry, this variant meets our criteria to be classified as pathogenic for autosomal recessive hearing loss with EVA or Pendred syndrome.
Division of Hearing and Balance Research,National Hospital Organization Tokyo Medical Center RCV000005096 SCV000611823 pathogenic Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 2017-07-01 criteria provided, single submitter clinical testing
Invitae RCV001057908 SCV001222431 pathogenic not provided 2020-09-17 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 721 of the SLC26A4 protein (p.Thr721Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs121908363, ExAC 0.04%). This variant has been observed in individual(s) with enlarged vestibular aqueduct and hearing loss (PMID: 10190331, 26763877, 28964290). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4826). This variant has been reported to affect SLC26A4 protein function (PMID: 20826203). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001057908 SCV001774332 pathogenic not provided 2021-04-28 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect; variant protein is retained in the cytoplasm leading to the loss of normal anion transporter activity (Ishihara et al., 2010); This variant is associated with the following publications: (PMID: 15905611, 32447495, 31589614, 30275481, 31541171, 31599023, 31427586, 12112665, 18813951, 26763877, 24599119, 20826203, 23185506, 17949297, 11748854, 15355436, 21704276, 27176802, 20597900, 29871341, 28964290, 10190331, 12676893, 26004784, 14508505, 25266519, 17443271)
OMIM RCV000005096 SCV000025272 pathogenic Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 2003-12-01 no assertion criteria provided literature only
OMIM RCV000005097 SCV000025273 pathogenic Pendred syndrome 2003-12-01 no assertion criteria provided literature only
Counsyl RCV000005097 SCV000221106 pathogenic Pendred syndrome 2016-05-24 no assertion criteria provided clinical testing
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery,Institute of Otolaryngology, Chinese PLA General Hospital RCV000005096 SCV000902361 likely pathogenic Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 2019-02-26 no assertion criteria provided case-control
National Institute of Sensory Organs,National Hospital Organization Tokyo Medical Center RCV000005096 SCV000994908 affects Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 2019-08-20 no assertion criteria provided clinical testing in vitro experiment
Natera, Inc. RCV000005097 SCV001459940 pathogenic Pendred syndrome 2020-09-16 no assertion criteria provided clinical testing

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