ClinVar

Description

Variant summary: MYO15A c.6437G>A (p.Arg2146Gln) results in a conservative amino acid change located in the MyTH4 domain (IPR000857) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 248620 control chromosomes (gnomAD). c.6437G>A has been reported in the literature in compound heterozygous state in two siblings, who carried a likely pathogenic variant in trans, and were affected with profound, bilateral nonsyndromic hearing loss (Woo_2013), in addition the variant was also reported in heterozygous state (i.e. without specifying a variant in trans) in an individual with nonsyndromic hearing loss in the setting of a multigene panel testing (Sloan-Heggen_2015). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted a clinical-significance assessment for this variant to ClinVar after 2014 and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.