Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004113648 | SCV003583979 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-10-01 | criteria provided, single submitter | clinical testing | The c.1354G>A (p.G452S) alteration is located in exon 9 (coding exon 8) of the FLNA gene. This alteration results from a G to A substitution at nucleotide position 1354, causing the glycine (G) at amino acid position 452 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003777733 | SCV004589022 | uncertain significance | Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia | 2022-12-12 | criteria provided, single submitter | clinical testing | 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FLNA protein function. This variant has not been reported in the literature in individuals affected with FLNA-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.001%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 452 of the FLNA protein (p.Gly452Ser). 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. |
| Gene |
RCV004725590 | SCV005333311 | uncertain significance | not provided | 2024-03-11 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |