ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.1198del (p.Cys400fs) (rs397516413)

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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 RCV000036426 SCV000060081 pathogenic Rare genetic deafness 2017-08-17 criteria provided, single submitter clinical testing The p.Cys400fs variant in SLC26A4 has been reported in the homozygous or compoun d heterozygous state in six individuals with hearing loss or Pendred syndrome (V an Hauwe 1998 and Fugazzola 2000 reported as 1421delT; Everett 1997 and Lopez-Bi gas 2001 reported as 1197delT; Chen 2011). The variant has been identified in 3/ 111286 European chromosomes, 2/33560 Latino chromosomes, and 1/30782 South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinst itute.org; dbSNP rs760012666); such low frequencies in the general population ar e consistent with the carrier frequency for recessive hearing loss. This framesh ift variant is predicted to alter the protein?s amino acid sequence beginning at codon 400 and lead to a premature termination codon 32 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. In s ummary, this variant meets criteria to be classified as pathogenic for autosomal recessive hearing loss with enlarged vestibular aqueducts or Pendred syndrome.
Counsyl RCV000169097 SCV000220286 likely pathogenic Pendred syndrome 2014-04-30 criteria provided, single submitter literature only
Invitae RCV000802527 SCV000942363 pathogenic not provided 2018-11-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys400Valfs*32) in the SLC26A4 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs760012666, ExAC 0.006%). This variant has been observed to segregate with Pendred syndrome in several individuals and families (PMID: 9398842, 24224479). This variant is also known as 1421delT in the literature. ClinVar contains an entry for this variant (Variation ID: 43494). 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.
Laboratory of Prof. Karen Avraham,Tel Aviv University RCV000169097 SCV000281986 pathogenic Pendred syndrome 2016-02-16 no assertion criteria provided research Congenital, moderate-profound HL
Laboratory of Prof. Karen Avraham,Tel Aviv University RCV000225034 SCV000281987 pathogenic Enlarged vestibular aqueduct 2016-02-16 no assertion criteria provided research Congenital, moderate-profound HL
Hereditary Research Laboratory,Bethlehem University RCV000169097 SCV000538115 pathogenic Pendred syndrome 2016-06-04 no assertion criteria provided research congenital, severe

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