Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003103894 | SCV001196451 | likely pathogenic | not provided | 2021-08-31 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exon(s) 3-5 of the FH gene. This variant would be expected to be in-frame, preserving the integrity of the reading frame. A similar copy number variant has been observed in individual(s) with clinical features of hereditary leiomyomatosis and renal cell cancer (HLRCC) (PMID: 28300276; Invitae). This variant disrupts the p.Asn107 amino acid residue in FH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11865300, 15937070, 21445611, 22473397, 22764886, 24625422). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |