ClinVar Miner

Submissions for variant NM_144612.6(LOXHD1):c.5002C>T (p.Arg1668Ter) (rs961865375)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000669718 SCV000794497 likely pathogenic Deafness, autosomal recessive 77 2017-09-27 criteria provided, single submitter clinical testing
Invitae RCV000800277 SCV000939982 pathogenic not provided 2018-08-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1668*) in the LOXHD1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with LOXHD1-related disease. Loss-of-function variants in LOXHD1 are known to be pathogenic (PMID: 19732867, 21465660, 25792669). For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000825566 SCV000966895 pathogenic Rare genetic deafness 2018-03-02 criteria provided, single submitter clinical testing The p.Arg1668X variant in the LOXHD1 gene has been identified in our laboratory in 1 individual with hearing loss and a second pathogenic variant in LOXHD1 (or ientation not yet tested). This variant has been identified in 7/58016 European and 4/23958 Latino chromosomes by the Genome Aggregation Database (gnomAD, http: //gnomad.broadinstitute.org; dbSNP rs961865375). Although this variant has been seen in the general population, its frequency is low enough to be consistent wit h a recessive carrier frequency. This nonsense variant leads to a premature term ination codon at position 1668 which is predicted to lead to a truncated or abse nt protein. In summary, this variant meets criteria to be classified as pathogen ic for autosomal recessive hearing loss based on the predicted impact of the var iant, low frequency in the general population and the presence of this variant w ith another LOXHD1 nonsense variant in an affected individual. ACMG/AMP Criteria applied: PVS1; PM3_Supporting; PM2_Supporting.

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