Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002553244 | SCV001215142 | uncertain significance | not provided | 2022-03-29 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 330 of the FH protein (p.Thr330Ala). This variant is present in population databases (rs776313200, 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: 847461). 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. 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 | RCV003160398 | SCV003855150 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-23 | criteria provided, single submitter | clinical testing | The p.T330A variant (also known as c.988A>G), located in coding exon 7 of the FH gene, results from an A to G substitution at nucleotide position 988. The threonine at codon 330 is replaced by alanine, an amino acid with 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. |