Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001205714 | SCV001376984 | pathogenic | Fanconi anemia | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change affects the initiator methionine of the FANCL mRNA. The next in-frame methionine is located at codon 74. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individuals with clinical features of Fanconi anemia (PMID: 33727708; Invitae). ClinVar contains an entry for this variant (Variation ID: 936826). This variant disrupts the E2-like fold (ELF) domain of the FANCL protein, which is required for its interaction with the FANCB-FAAP100 complex as well as for non-covalent binding to ubiquitin (PMID: 26149689, 27986371). While functional studies have not been performed to directly test the effect of this variant on FANCL protein function, this suggests that disruption of this region of the protein is causative of disease. For these reasons, this variant has been classified as Pathogenic. |