Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002234965 | SCV000943854 | uncertain significance | Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1515 of the FLNA protein (p.Arg1515Gln). This variant is present in population databases (rs782597696, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with FLNA-related conditions. ClinVar contains an entry for this variant (Variation ID: 649109). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FLNA protein function with a negative predictive value of 95%. 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 | RCV002336626 | SCV002639925 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2020-11-02 | criteria provided, single submitter | clinical testing | The p.R1515Q variant (also known as c.4544G>A), located in coding exon 26 of the FLNA gene, results from a G to A substitution at nucleotide position 4544. The arginine at codon 1515 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, glutamine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Prevention |
RCV004735810 | SCV005354945 | uncertain significance | FLNA-related disorder | 2024-07-03 | no assertion criteria provided | clinical testing | The FLNA c.4544G>A variant is predicted to result in the amino acid substitution p.Arg1515Gln. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |