Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001295990 | SCV001484944 | pathogenic | Birt-Hogg-Dube syndrome | 2023-09-12 | criteria provided, single submitter | clinical testing | This sequence change affects the initiator methionine of the FLCN mRNA. The next in-frame methionine is located at codon 54. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individual(s) with clinical features of Birt-Hogg-Dubé syndrome and/or colorectal cancer (PMID: 17034545, 19801896, 22146830, 28944238). ClinVar contains an entry for this variant (Variation ID: 999927). This variant disrupts a region of the FLCN protein in which other variant(s) (p.Cys11Trp) have been determined to be pathogenic (Invitae; external communication). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |