Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002536030 | SCV000965507 | likely pathogenic | not provided | 2023-06-02 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects FH function (PMID: 21560188). 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. ClinVar contains an entry for this variant (Variation ID: 666168). This variant is also known as c.815T>C (p.Leu272Pro). This missense change has been observed in individuals with hereditary leiomyomatosis and renal cell carcinoma (PMID: 21398687, 28300276). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 315 of the FH protein (p.Leu315Pro). |
Mendelics | RCV004698852 | SCV005200760 | likely pathogenic | Hereditary cancer | 2024-08-12 | criteria provided, single submitter | clinical testing |