Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001061044 | SCV001225768 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with threonine at codon 2705 of the FLNC protein (p.Ile2705Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs553714847, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. 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. 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. |
| Ambry Genetics | RCV004031941 | SCV004871168 | uncertain significance | Cardiovascular phenotype | 2023-12-27 | criteria provided, single submitter | clinical testing | The c.8114T>C (p.I2705T) alteration is located in exon 48 (coding exon 48) of the FLNC gene. This alteration results from a T to C substitution at nucleotide position 8114, causing the isoleucine (I) at amino acid position 2705 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |