Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Blueprint Genetics | RCV000788573 | SCV000927728 | uncertain significance | not provided | 2018-06-06 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001065013 | SCV001229951 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-08-22 | criteria provided, single submitter | clinical testing | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FLNC protein function. 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. ClinVar contains an entry for this variant (Variation ID: 636671). This missense change has been observed in individual(s) with frontotemporaldementia (PMID: 26555887). This variant is present in population databases (rs761881020, gnomAD 0.002%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1370 of the FLNC protein (p.Arg1370Gln). |
Gene |
RCV000788573 | SCV002504267 | likely benign | not provided | 2020-02-07 | criteria provided, single submitter | clinical testing | See Variant Classification Assertion Criteria. |
Ambry Genetics | RCV002325491 | SCV002626912 | uncertain significance | Cardiovascular phenotype | 2020-10-13 | criteria provided, single submitter | clinical testing | The p.R1370Q variant (also known as c.4109G>A), located in coding exon 23 of the FLNC gene, results from a G to A substitution at nucleotide position 4109. The arginine at codon 1370 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been reported in a frontotemporal dementia cohort (Janssens J et al. Acta Neuropathol Commun, 2015 Nov;3:68). This amino acid position is not well conserved in available vertebrate species. 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. |