Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002314183 | SCV000738440 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2016-01-13 | criteria provided, single submitter | clinical testing | The p.P277L variant (also known as c.830C>T), located in coding exon 4 of the FLNA gene, results from a C to T substitution at nucleotide position 830. The proline at codon 277 is replaced by leucine, an amino acid with some similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6487 samples with coverage at this position. This amino acid position is highly 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 variant remains unclear. |
| ARUP Laboratories, |
RCV003117428 | SCV003800500 | uncertain significance | not provided | 2022-03-11 | criteria provided, single submitter | clinical testing | The FLNA c.830C>T; p.Pro277Leu variant (rs1557179540), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 519566). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. The proline at codon 277 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.564). Due to limited information, the clinical significance of this variant is uncertain at this time. |
| Labcorp Genetics |
RCV003767792 | SCV004568532 | uncertain significance | Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia | 2024-01-20 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 277 of the FLNA protein (p.Pro277Leu). 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: 519566). 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. 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 |
RCV003117428 | SCV005369934 | uncertain significance | not provided | 2023-05-30 | criteria provided, single submitter | clinical testing | 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 |