ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.1258A>T (p.Lys420Ter) (rs782539587)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery,Institute of Otolaryngology, Chinese PLA General Hospital RCV000770845 SCV000902346 pathogenic Deafness, autosomal recessive 2 2019-02-26 no assertion criteria provided case-control
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000601432 SCV000710850 pathogenic Rare genetic deafness 2017-07-11 criteria provided, single submitter clinical testing The p.Lys420X variant in MYO7A has been identified in the homozygous or compound heterozygous state in 6 individuals with clinical features of Usher syndrome (B onnet 2016, Le Quesne Stabej 2012, Shahzad 2013). In one study, this variant was identified in the homozygous state in 4 separate families of Pakistani descent with histories of consanguinity and segregated in over 10 affected family member s (Shahzad 2013). It has also been identified in 4/235612 chromosomes by the Gen ome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs7825 39587); however, this frequency is low enough to be consistent with a carrier fr equency for recessive Usher syndrome. The p.Lys420X nonsense variant leads to a premature termination codon at position 420, which is predicted to lead to a tru ncated or absent protein. Loss of MYO7A gene function is an established disease mechanism for autosomal recessive Usher syndrome. In summary, this variant meet s criteria to be classified as pathogenic for autosomal recessive Usher syndrome based on the predicted impact of the variant, homozygosity and compound zygosit y in affected individuals, segregation evidence, and low frequency in the genera l population.

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