Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000817309 | SCV000957861 | pathogenic | Hereditary hyperferritinemia with congenital cataracts; Neuroferritinopathy | 2020-10-11 | criteria provided, single submitter | clinical testing | The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant occurs in a non-coding region of the FTL gene. It does not change the encoded amino acid sequence of the FTL protein. For these reasons, this variant has been classified as Pathogenic. This nucleotide change is located in a region of the FTL 5'UTR where a significant number of previously reported deleterious variants has been observed (PMID: 19800271, 7493028, 23421845, 10383191, 22881709, 9226182), and the mechanism of action suggest that this c.-164C>A change is also likely to be deleterious. Experimental studies and prediction algorithms are not available for this specific variant (c.-164C>A), although studies indicate that other changes at this position (c.-164C>G, c.-164C>T, c.-164delC) disrupt binding of Iron Regulatory Proteins (IRPs) to the FTL 5' UTR (PMID: 2336358, 23421845). This variant has been observed in individual(s) with clinical features of hereditary hyperferritinemia-cataract syndrome (PMID: 9414313, Invitae). It has also been observed to segregate with disease in related individuals. This variant is also known as +36C>A. ClinVar contains an entry for this variant (Variation ID: 16481). |
| OMIM | RCV000017945 | SCV000038224 | pathogenic | Hereditary hyperferritinemia with congenital cataracts | 2013-02-19 | no assertion criteria provided | literature only |