Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002553885 | SCV001225263 | uncertain significance | not provided | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 215 of the FH protein (p.His215Leu). 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: 855318). 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 not expected to disrupt FH protein function with a negative 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, |
RCV002255615 | SCV002535567 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-22 | criteria provided, single submitter | curation | |
Ambry Genetics | RCV002255615 | SCV002656799 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-13 | criteria provided, single submitter | clinical testing | The p.H215L variant (also known as c.644A>T), located in coding exon 5 of the FH gene, results from an A to T substitution at nucleotide position 644. The histidine at codon 215 is replaced by leucine, an amino acid with similar properties. This amino acid position is not 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. |