ClinVar

Description

Variant summary: The variant involves the deletion of exons 1-2 in the MPV17 gene. A presumed nomenclature of c.(?_-52)_(70+1_71-1)del has been designated for the purposes of this classification. The exact breakpoint at the 5' end of this variant is unknown, therefore this deletion may extend upstream of the annotated region of this gene. Although the exact breakpoints of this deletion are not known, it is predicted to remove the initiation codon and result in an absence of protein or a truncation of the encoded protein due to translation initiation at a downstream site. The variant was absent in 120,780 control chromosomes in the gnomAD database (Structural Variants v4.0 dataset). To our knowledge, no occurrence of c.(?_-52)_(70+1_71-1)del in individuals affected with Mitochondrial DNA Depletion Syndrome - MPV17 Related, and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as pathogenic.