Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Foundation for Research in Genetics and Endocrinology, |
RCV004789507 | SCV001446312 | uncertain significance | Atelosteogenesis type III; Atelosteogenesis type I; Larsen syndrome | 2020-10-13 | criteria provided, single submitter | clinical testing | A heterozygous missense variation in exon 47 of the FLNB gene that results in the amino acid substitution of Isoleucine for Valine at codon 2606 was detected. The observed variant c.7816G>A (p.Val2606Ile) has not been reported in the 1000 genomes and has a minor allele frequency of 0.004% in the gnomAD database. The in silico prediction of the variant is damaging by LRT and MutationTaster2. The reference codon is conserved across mammals. In summary, the variant meets our criteria to be classified as a variant of uncertain significance. |
Labcorp Genetics |
RCV002542853 | SCV002935224 | uncertain significance | not provided | 2024-10-16 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 2575 of the FLNB protein (p.Val2575Ile). This variant is present in population databases (rs369949841, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with FLNB-related conditions. ClinVar contains an entry for this variant (Variation ID: 986736). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt FLNB protein function with a negative predictive value of 80%. 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. |
Ambry Genetics | RCV002541633 | SCV003547969 | uncertain significance | Inborn genetic diseases | 2021-08-09 | criteria provided, single submitter | clinical testing | The c.7723G>A (p.V2575I) alteration is located in exon 46 (coding exon 46) of the FLNB gene. This alteration results from a G to A substitution at nucleotide position 7723, causing the valine (V) at amino acid position 2575 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |