Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mendelics | RCV000989668 | SCV001140200 | likely pathogenic | Fanconi anemia complementation group A | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001858712 | SCV002111612 | likely pathogenic | Fanconi anemia | 2023-06-14 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg1400 amino acid residue in FANCA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15643609, 21273304, 24584348, 28102861, 28717661, 29098742). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FANCA protein function. ClinVar contains an entry for this variant (Variation ID: 803290). This missense change has been observed in individuals with Fanconi anemia (PMID: 28717661, 30792206, 34585473). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 1400 of the FANCA protein (p.Arg1400Pro). |
Leiden Open Variation Database | RCV001256421 | SCV001425871 | uncertain significance | not provided | 2020-02-28 | no assertion criteria provided | curation | Curator: Arleen D. Auerbach. Submitter to LOVD: Daniela Pilonetto. |