MET was first reported in relation to autosomal recessive nonsyndromic hearing loss in 2015 (Mujtaba et al., PMID: 25941349). This association was made using case-level data only. Three missense variants that have been reported in 3 probands in 3 publications (PMIDs: 25941349, 27717089, 31801140) are included in this curation. Only one missense variant was scored as the probands with the other variant had inconsistent phenotypes with nonsyndromic hearing loss and the minor allele frequency of the other variant was too high to be considered pathogenic. One missense variant in this gene segregated with disease in 8 additional family members (PMID: 25941349). While no variant-level functional evidence has been published, this gene-disease association is supported by an expression study, a biochemical study consistent with the phenotype, and an animal model (PMID: 27488639). In summary, there is limited evidence to support this gene-disease association. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease association. This classification was approved by the ClinGen Hearing Loss Gene Curation Expert Panel on the meeting date 3/26/2021 (SOP Version 8). This gene-disease pair was originally evaluated by the ClinGen Hearing Loss GCEP on 12/19/2017. It was reevaluated on 3/26/2021. As a result of this reevaluation, the classification did not change.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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