Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003117710 | SCV003790735 | pathogenic | not provided | 2021-08-12 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exon(s) 8-10 of the FH gene, which includes the termination codon. This deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. While this deletion is not anticipated to lead to nonsense mediated decay, it is expected to alter mRNA translation or result in a truncated protein product. This variant has not been reported in the literature in individuals affected with FH-related conditions. This variant disrupts a region of the FH protein in which other variant(s) (p.Glu495Valfs*2, p.Trp500*, p.Gly490Alafs*12, p.Leu492Hisfs*6) have been determined to be pathogenic (PMID: 9635293, 12772087, 16597677, 21398687, 21404119; 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. For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001033601 | SCV001196908 | pathogenic | Fumarase deficiency | 2019-02-15 | flagged submission | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 8-10 of the FH gene. The 5' boundary is likely confined to intron 7. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. This variant has not been reported in the literature in individuals with FH-related conditions. This variant disrupts the C-terminus of the FH protein. Other variant(s) that disrupt this region (p.Gly490Alafs*12, p.Leu492Hisfs*6, p.Glu495Valfs*2, and p.Trp500*) have been determined to be pathogenic (PMID: 12772087, 21404119, 16597677, 9635293, 21398687, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. |