Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genomic Diagnostic Laboratory, |
RCV000408857 | SCV000484871 | pathogenic | Blepharophimosis, ptosis, and epicanthus inversus syndrome | 2016-11-03 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002523842 | SCV003525370 | pathogenic | not provided | 2022-06-17 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the FOXL2 protein in which other variant(s) (p.Pro307Hisfs*52) have been determined to be pathogenic (PMID: 11468277). 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: 369912). This variant is also known as c.576_577insC. This premature translational stop signal has been observed in individual(s) with blepharophimosis, ptosis, and epicanthus inversus syndrome (PMID: 18642388, 31048069). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys193Glnfs*46) in the FOXL2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 184 amino acid(s) of the FOXL2 protein. |
| Ambry Genetics | RCV003362773 | SCV004079784 | pathogenic | Inborn genetic diseases | 2023-08-16 | criteria provided, single submitter | clinical testing | The c.576dupC (p.K193Qfs*46) alteration, located in exon 1 (coding exon 1) of the FOXL2 gene, consists of a duplication of C at position 576, causing a translational frameshift with a predicted alternate stop codon after 46 amino acids. Frameshifts/Premature stop codons are typically deleterious in nature; however, because FOXL2 is a single-exon gene this alteration is not expected to trigger nonsense-mediated mRNA decay and a(n) altered/truncated protein could still be expressed (Maquat, 2004). This alteration impacts/removes the last 183 amino acids of the protein and the exact functional impact of these amino acids is unknown at this time. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been reported in multiple individuals and their family members with clinical features consistent with FOXL2-related blepharophimosis, epicanthus inversus, and ptosis (Beysen, 2008; Chacón-Camacho, 2019). Based on the available evidence, this alteration is classified as pathogenic. |