Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001011297 | SCV001171599 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-12-22 | criteria provided, single submitter | clinical testing | The c.1390G>A variant (also known as p.G464R), located in coding exon 9 of the FH gene, results from a G to A substitution at nucleotide position 1390. The amino acid change results in glycine to arginine at codon 464, an amino acid with dissimilar properties. This change occurs in the last base pair of coding exon 9, which makes it likely to have some effect on normal mRNA splicing; however, RNA studies have demonstrated that this alteration does not result in abnormal splicing in a set of samples tested (Ambry internal data). Based on internal structural assessment, p.G464R is anticipated to result in a significant decrease in structural stability (Ambry internal data). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |