Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003007508 | SCV003303265 | uncertain significance | Fanconi anemia | 2022-08-09 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 FANCA protein function. This variant has not been reported in the literature in individuals affected with FANCA-related conditions. This variant is present in population databases (rs761902950, gnomAD 0.006%). This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 1236 of the FANCA protein (p.Gln1236Glu). |
| Ambry Genetics | RCV004978467 | SCV005581129 | uncertain significance | Inborn genetic diseases | 2024-11-23 | criteria provided, single submitter | clinical testing | The p.Q1236E variant (also known as c.3706C>G), located in coding exon 37 of the FANCA gene, results from a C to G substitution at nucleotide position 3706. The glutamine at codon 1236 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |