Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001894088 | SCV002127238 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2021-05-31 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with FLNC-related conditions. This sequence change replaces isoleucine with valine at codon 1946 of the FLNC protein (p.Ile1946Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. |
| Ambry Genetics | RCV004039636 | SCV005017745 | uncertain significance | Cardiovascular phenotype | 2024-03-13 | criteria provided, single submitter | clinical testing | The p.I1946V variant (also known as c.5836A>G), located in coding exon 35 of the FLNC gene, results from an A to G substitution at nucleotide position 5836. The isoleucine at codon 1946 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. |