Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001590258 | SCV001826056 | uncertain significance | not provided | 2020-08-10 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Labcorp Genetics |
RCV001590258 | SCV003197692 | pathogenic | not provided | 2022-08-21 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the FH protein in which other variant(s) (p.Ala486Asp) have been determined to be pathogenic (PMID: 20109895; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 1217999). This variant has not been reported in the literature in individuals affected with FH-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.1456_1458del, results in the deletion of 1 amino acid(s) of the FH protein (p.Ala486del), but otherwise preserves the integrity of the reading frame. |