Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001017058 | SCV001178082 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-16 | criteria provided, single submitter | clinical testing | The p.R343Q variant (also known as c.1028G>A), located in coding exon 7 of the FH gene, results from a G to A substitution at nucleotide position 1028. The arginine at codon 343 is replaced by glutamine, an amino acid with highly similar properties. 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. |
Invitae | RCV002549447 | SCV001386221 | uncertain significance | not provided | 2024-01-03 | 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 343 of the FH protein (p.Arg343Gln). This variant is present in population databases (rs756990249, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with FH-related conditions. ClinVar contains an entry for this variant (Variation ID: 822038). 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 expected to disrupt FH protein function with a positive predictive value of 95%. 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. |
Sema4, |
RCV001017058 | SCV002535132 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-21 | criteria provided, single submitter | curation | |
Natera, |
RCV001214537 | SCV002085305 | uncertain significance | Fumarase deficiency | 2021-10-11 | no assertion criteria provided | clinical testing |