Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002528327 | SCV000632457 | uncertain significance | not provided | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 128 of the FH protein (p.Ala128Thr). This variant is not present in population databases (gnomAD no frequency). 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: 460353). 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) has been performed at Invitae 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 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. |
| Fulgent Genetics, |
RCV000765097 | SCV000896306 | uncertain significance | Fumarase deficiency; Hereditary leiomyomatosis and renal cell cancer | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002358479 | SCV002623250 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-10 | criteria provided, single submitter | clinical testing | The p.A128T variant (also known as c.382G>A), located in coding exon 4 of the FH gene, results from a G to A substitution at nucleotide position 382. The alanine at codon 128 is replaced by threonine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV002528327 | SCV005080250 | uncertain significance | not provided | 2024-04-05 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Natera, |
RCV000530788 | SCV002085873 | uncertain significance | Fumarase deficiency | 2021-04-06 | no assertion criteria provided | clinical testing |