ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.284A>T (p.Tyr95Phe) (rs797044489)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000151475 SCV000199538 likely pathogenic Rare genetic deafness 2017-12-26 criteria provided, single submitter clinical testing The p.Tyr95Phe variant in MYO7A has been identified in 1 child with hearing loss who was compound heterozygous with a pathogenic nonsense variant in MYO7A. Thes e variants segregated in an affected sibling. Neither sibling was reported to ha ve balance problems or delayed walking, though formal eye evaluations had not oc curred yet at the time of testing. This variant was absent from large population studies. A different amino acid change at the same position, p.Tyr95Cys, was id entified in trans with a nonsense variant in MYO7A in two siblings with Usher sy ndrome (Bujakowska 2014). This variant is located in the last three bases of the exon, which is part of the 5? splice region. Computational tools do not predict altered splicing. However computational prediction tools and conservation anal yses for the amino acid change suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. I n summary, although additional studies are required to fully establish its clini cal significance and to determine whether it could cause Usher syndrome or atypi cal Usher syndrome, this variant is likely pathogenic for autosomal recessive he aring loss. ACMG/AMP Criteria applied: PM2, PM3, PM5, PP3.

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