Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001371932 | SCV001568516 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2021-09-19 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with isoleucine at codon 1148 of the FLNC protein (p.Thr1148Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. |
| Ambry Genetics | RCV004037518 | SCV005017781 | uncertain significance | Cardiovascular phenotype | 2023-09-24 | criteria provided, single submitter | clinical testing | The p.T1148I variant (also known as c.3443C>T), located in coding exon 21 of the FLNC gene, results from a C to T substitution at nucleotide position 3443. The threonine at codon 1148 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |