ClinVar

Description

A variant of uncertain significance has been identified in the MIB1 gene. The c.939dupA variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.939dupA variant causes a shift in reading frame starting at codon alanine 314, changing it to a serine, and creating a premature stop codon at position 24 of the new reading frame, denoted p.Ala314SerfsX24. This variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. However, few other loss of function variants in the MIB1 gene have been reported in Human Gene Mutation Database in association with MIB1-associated disorders (Stenson et al., 2014), indicating that there is not enough evidence supporting haploinsufficiency as a disease mechanism for MIB1-related disorders.