Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001774522 | SCV002001973 | uncertain significance | not provided | 2023-11-07 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Labcorp Genetics |
RCV002544157 | SCV003519068 | uncertain significance | Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia | 2022-06-22 | 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: 1315272). This variant has not been reported in the literature in individuals affected with FLNA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 226 of the FLNA protein (p.Arg226Gln). |
| ARUP Laboratories, |
RCV001774522 | SCV003799525 | uncertain significance | not provided | 2022-05-06 | criteria provided, single submitter | clinical testing | The FLNA c.677G>A; p.Arg226Gln variant (rs2067772868), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 1315272). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. The arginine at codon 226 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.655). Due to limited information, the clinical significance of this variant is uncertain at this time. |
| Neuberg Centre For Genomic Medicine, |
RCV004785308 | SCV005400928 | uncertain significance | Cardiac valvular dysplasia, X-linked | criteria provided, single submitter | clinical testing | The observed missense variant c.677G>A(p.Arg226Gln) in the FLNA gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant has been reported to the ClinVar database as Uncertain Significance. However, no details are available for independent assessment. This variant is absent in the gnomAD Exomes. The amino acid Arg at position 226 is changed to a Gln changing protein sequence and it might alter its composition and physico-chemical properties. Multiple lines of computational evidence (Polyphen - Possibly Damaging, SIFT - Damaging and MutationTaster - Disease causing) predict a damaging effect on protein structure and function for this variant. The residue is conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. |