Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000818294 | SCV000958897 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2018-11-30 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with methionine at codon 2392 of the FLNC protein (p.Ile2392Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FLNC-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 | RCV004028951 | SCV003973104 | uncertain significance | Cardiovascular phenotype | 2023-04-25 | criteria provided, single submitter | clinical testing | The c.7176C>G (p.I2392M) alteration is located in exon 43 (coding exon 43) of the FLNC gene. This alteration results from a C to G substitution at nucleotide position 7176, causing the isoleucine (I) at amino acid position 2392 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |