Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001591075 | SCV000544289 | uncertain significance | not provided | 2025-01-27 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 206 of the FH protein (p.Val206Ile). This variant is present in population databases (rs763183520, gnomAD 0.004%). 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: 405938). Invitae Evidence 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 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. |
| Ambry Genetics | RCV001024965 | SCV001187065 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-01 | criteria provided, single submitter | clinical testing | The p.V206I variant (also known as c.616G>A), located in coding exon 5 of the FH gene, results from a G to A substitution at nucleotide position 616. The valine at codon 206 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly 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 |
RCV001591075 | SCV001814371 | uncertain significance | not provided | 2024-04-20 | 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 |
| Prevention |
RCV004555578 | SCV004120783 | uncertain significance | FH-related disorder | 2023-05-17 | criteria provided, single submitter | clinical testing | The FH c.616G>A variant is predicted to result in the amino acid substitution p.Val206Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0031% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-241672025-C-T) and is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/405938/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Baylor Genetics | RCV000460134 | SCV004197298 | uncertain significance | Fumarase deficiency | 2024-02-26 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV005018749 | SCV005644096 | uncertain significance | Fumarase deficiency; Hereditary leiomyomatosis and renal cell cancer | 2024-04-15 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV000460134 | SCV001455896 | uncertain significance | Fumarase deficiency | 2019-10-28 | no assertion criteria provided | clinical testing |