Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001349769 | SCV001544129 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-08-31 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1045370). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This variant is present in population databases (rs781671804, gnomAD 0.005%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2206 of the FLNC protein (p.Arg2206Gln). |
| Ambry Genetics | RCV003284241 | SCV004006275 | uncertain significance | Cardiovascular phenotype | 2023-06-09 | criteria provided, single submitter | clinical testing | The p.R2206Q variant (also known as c.6617G>A), located in coding exon 40 of the FLNC gene, results from a G to A substitution at nucleotide position 6617. The arginine at codon 2206 is replaced by glutamine, an amino acid with highly similar properties. This variant co-occurred with a truncating variant in the TTN gene in a family with dilated cardiomyopathy and myopathy (Cuenca S et al. J Heart Lung Transplant, 2016 May;35:625-35). This amino acid position is highly conserved in available vertebrate species. 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. |
| Prevention |
RCV003973213 | SCV004789159 | uncertain significance | FLNC-related disorder | 2024-01-09 | criteria provided, single submitter | clinical testing | The FLNC c.6617G>A variant is predicted to result in the amino acid substitution p.Arg2206Gln. This variant has been reported, along with a truncating TTN variant, in a family with dilated cardiomyopathy (Cuenca et al. 2016. PubMed ID: 26899768). This variant has not been reported in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |