ClinVar Miner

Submissions for variant NM_138691.2(TMC1):c.1141T>A (p.Tyr381Asn) (rs749491943)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000416069 SCV000493660 uncertain significance not provided 2016-07-31 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000215864 SCV000272503 likely pathogenic Rare genetic deafness 2017-11-02 criteria provided, single submitter clinical testing The p.Tyr381Asn variant in TMC1 has been reported in 2 individuals with hearing loss in compound heterozygosity with another pathogenic TMC1 variant and segrega ted in an affected family member (Sommen 2016, LMM data). This variant has been identified in 7/126578 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs749491943); however, its freq uency is low enough to be consistent with a recessive carrier frequency for hear ing loss. Computational prediction tools and conservation analysis suggest that the p.Tyr381Asn variant may impact the protein, though this information is not p redictive enough to determine pathogenicity. In summary, although additional stu dies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive nonsyndromic sensorineural hearing los s. ACMG/AMP criteria applied: PM3, PM2, PP1, PP3.

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