Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001369416 | SCV001565855 | uncertain significance | Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia | 2022-01-07 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 1060042). 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 0.004%). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 877 of the FLNA protein (p.Ala877Pro). |
| Ambry Genetics | RCV002438861 | SCV002745693 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-03-23 | criteria provided, single submitter | clinical testing | The p.A877P variant (also known as c.2629G>C), located in coding exon 17 of the FLNA gene, results from a G to C substitution at nucleotide position 2629. The alanine at codon 877 is replaced by proline, an amino acid with highly similar properties. Based on data from gnomAD, the C allele has an overall frequency of 0.0011% (2/181304) total alleles studied, with 0 hemizygote(s) observed. The highest observed frequency was 0.0037% (1/27377) of Latin American alleles. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV004794534 | SCV005415315 | uncertain significance | not provided | 2024-05-23 | 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 |