Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000813817 | SCV000954194 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-05-01 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 657244). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This variant is present in population databases (rs768820218, gnomAD 0.0009%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1046 of the FLNC protein (p.Pro1046Leu). |
Ce |
RCV002292584 | SCV002586194 | uncertain significance | not provided | 2022-09-01 | criteria provided, single submitter | clinical testing | FLNC: PM2:Supporting, PS2:Supporting |
Ambry Genetics | RCV003279094 | SCV004004625 | uncertain significance | Cardiovascular phenotype | 2023-05-11 | criteria provided, single submitter | clinical testing | The p.P1046L variant (also known as c.3137C>T), located in coding exon 20 of the FLNC gene, results from a C to T substitution at nucleotide position 3137. The proline at codon 1046 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. 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. |