ClinVar Miner

Submissions for variant NM_000146.4(FTL):c.-168G>A

gnomAD frequency: 0.00001  dbSNP: rs398124635
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001380757 SCV001578914 pathogenic Hereditary hyperferritinemia with congenital cataracts; Neuroferritinopathy 2024-10-07 criteria provided, single submitter clinical testing 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. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with hyperferritinemia-cataract syndrome (PMID: 9226182, 16518306, 28746593). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 16476). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001723575 SCV005870245 likely pathogenic not provided 2024-08-21 criteria provided, single submitter clinical testing Identified in a patient with hyperferritinemia-cataract syndrome who also harbored a heterozygous variant in the HFE gene in published literature (PMID: 28746593); This variant is associated with the following publications: (PMID: 23421845, 30678075, 26147798, 21907119, 31211687, 11703332, 20624502, 17951290, 20578964, 9226182, 16518306, 28746593)
OMIM RCV000017940 SCV000038219 pathogenic Hereditary hyperferritinemia with congenital cataracts 2013-02-19 no assertion criteria provided literature only
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001723575 SCV001951344 pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001723575 SCV001970766 pathogenic not provided no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004751214 SCV005355325 pathogenic FTL-related disorder 2024-07-24 no assertion criteria provided clinical testing The FTL c.-168G>A variant is located in the 5' untranslated region. This variant, also known in the literature as Pavia 1, +32, and G32A, has been reported in multiple families with elevated serum ferritin and cataract (Family 1, Cazzola et al. 1997. PubMed ID: 9226182; Girelli et al. 2001. PubMed ID: 11703332; Case 1, Petroni et al. 2017. PubMed ID: 28746593; Vanita et al. 2006. PubMed ID: 16518306; Family 1, Volkmann et al. 2019. PubMed ID: 31211687). This variant occurs within a highly conserved non-coding region known as the iron regulatory element and other variants within this region, including additional variants at the +32 position (G32T and G32C) have also been found in patients with FTL-related disorders (Cazzola et al. 1997. PubMed ID: 9226182; Girelli et al. 2001. PubMed ID: 11703332; Volkmann et al. 2019. PubMed ID: 31211687). This variant has not been reported in gnomAD, indicating this variant is rare. Based on this evidence, we interpret this variant pathogenic.

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