Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001352034 | SCV001546557 | uncertain significance | Fanconi anemia | 2022-09-30 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 409 of the FANCB protein (p.Arg409Gln). This variant is present in population databases (rs753030842, gnomAD 0.006%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with FANCB-related conditions. ClinVar contains an entry for this variant (Variation ID: 1047336). 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 FANCB protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
| Fulgent Genetics, |
RCV002476617 | SCV002796363 | uncertain significance | Fanconi anemia complementation group B; VACTERL association, X-linked, with or without hydrocephalus | 2022-02-03 | criteria provided, single submitter | clinical testing |