Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001201810 | SCV001372901 | uncertain significance | Fanconi anemia | 2024-01-18 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 121 of the FANCI protein (p.Leu121Pro). This variant is present in population databases (rs373184027, gnomAD 0.004%). This missense change has been observed in individual(s) with head and neck squamous cell carcinoma (PMID: 28678401). This missense change has been observed to co-occur in individuals with a different variant in FANCI that has been determined to be pathogenic (PMID: 28678401), but the significance of this finding is unclear. ClinVar contains an entry for this variant (Variation ID: 933569). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FANCI protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |