Diagnostic implications of pitfalls in causal variant identification based on 4577 molecularly characterized families.

ABSTRACT: Despite large sequencing and data sharing efforts, previously characterized pathogenic variants only account for a fraction of Mendelian disease patients, which highlights the need for accurate identification and interpretation of novel variants. In a large Mendelian cohort of 4577 molecularly characterized families, numerous scenarios in which variant identification and interpretation can be challenging are encountered. We describe categories of challenges that cover the phenotype (e.g. novel allelic disorders), pedigree structure (e.g. imprinting disorders masquerading as autosomal recessive phenotypes), positional mapping (e.g. double recombination events abrogating candidate autozygous intervals), gene (e.g. novel gene-disease assertion) and variant (e.g. complex compound inheritance).

SUBMITTER: AlAbdi L 

PROVIDER: S-EPMC10465531 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature