Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000556442 | SCV000626330 | uncertain significance | Fanconi anemia | 2024-10-31 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 592 of the FANCG protein (p.Tyr592His). This variant is present in population databases (rs768325047, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with FANCG-related conditions. ClinVar contains an entry for this variant (Variation ID: 456232). Invitae Evidence 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 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 FANCG protein function. 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. |
| Ambry Genetics | RCV004975630 | SCV005580632 | uncertain significance | Inborn genetic diseases | 2024-11-18 | criteria provided, single submitter | clinical testing | The p.Y592H variant (also known as c.1774T>C), located in coding exon 14 of the FANCG gene, results from a T to C substitution at nucleotide position 1774. The tyrosine at codon 592 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |