Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute for Genomic Medicine, |
RCV000735862 | SCV000863953 | likely pathogenic | Patellar hypoplasia; Knee dislocation; Limited knee flexion/extension | 2018-12-21 | criteria provided, single submitter | research | The c.5375_5377delAGG variant is a 3-bp deletion predicted to remove a highly conserved glutamic acid residue at position 1792 of the filamin B protein. This variant maps to one of numerous filamin domains in FLNB, but the local sequence context is not repetitive. Further, pathogenic mutations in two immediately adjacent filamin domains have been reported to the ClinVar database. In the gnomAD database, two out of 125,709 individuals are reported to be heterozygous for the c.5375_5377delAGG variant; however, only one of them has sequence data available for review. This variant segregates with disease in multiple affected family members. We therefore interpret it as likely pathogenic. |
Invitae | RCV001869012 | SCV002218987 | uncertain significance | not provided | 2023-11-10 | criteria provided, single submitter | clinical testing | This variant, c.5375_5377del, results in the deletion of 1 amino acid(s) of the FLNB protein (p.Glu1792del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has been observed in individual(s) with Larsen syndrome (PMID: 31836586). It has also been observed to segregate with disease in related individuals. This variant is also known as p.Glu1823del. ClinVar contains an entry for this variant (Variation ID: 599274). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |