Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001022133 | SCV001183831 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-08-30 | criteria provided, single submitter | clinical testing | The p.Q142E variant (also known as c.424C>G), located in coding exon 4 of the FH gene, results from a C to G substitution at nucleotide position 424. The glutamine at codon 142 is replaced by glutamic acid, 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 | RCV002551848 | SCV002250767 | uncertain significance | not provided | 2020-12-29 | 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. 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. This variant has not been reported in the literature in individuals with FH-related conditions. ClinVar contains an entry for this variant (Variation ID: 824719). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with glutamic acid at codon 142 of the FH protein (p.Gln142Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. |