ClinVar Miner

Submissions for variant NM_000441.1(SLC26A4):c.1342-2_1343dup (rs111033407)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000036440 SCV000060095 pathogenic Rare genetic deafness 2012-04-27 criteria provided, single submitter clinical testing The 1342-2_1343dupAGTC variant in SLC26A4 has been reported as a compound hetero zygous variant in 3 individuals with enlarged vestibular aqueducts (EVA) and has been identified by our laboratory in 3 other individuals each of whom has a sec ond pathogenic SLC26A4 variant (Choi 2009, LMM unpublished data). This variant l eads to the duplication of a conserved splice site at the beginning of exon 12, which could either deleteriously affect splicing of the transcript or cause a fr ameshift if 4 additional bases are included in the exon. In summary, this varian t meets our criteria to be classified as pathogenic (http://pcpgm.partners.org/L MM).
Invitae RCV001248593 SCV001422092 pathogenic not provided 2020-09-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu450Glyfs*19) in the SLC26A4 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in the compound heterozygous state in a family and individuals affected with hearing loss with enlargement of the vestibular aqueduct (PMID: 19204907, 15689455). This variant is also known as c.1340_1343dup and 1343–1344insAGTC in the literature. ClinVar contains an entry for this variant (Variation ID: 43506). 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.

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