Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002311116 | SCV000320066 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2020-04-23 | criteria provided, single submitter | clinical testing | The c.5635A>G (p.T1879A) alteration is located in exon 34 (coding exon 33) of the FLNA gene. This alteration results from a A to G substitution at nucleotide position 5635, causing the threonine (T) at amino acid position 1879 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001047797 | SCV001211778 | uncertain significance | Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia | 2023-10-09 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1879 of the FLNA protein (p.Thr1879Ala). This variant is not present in population databases (gnomAD no frequency). 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: 264261). 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. 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. |