ClinVar Miner

Submissions for variant NM_001458.5(FLNC):c.4222G>A (p.Glu1408Lys)

gnomAD frequency: 0.00005  dbSNP: rs965589915
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001061544 SCV001226289 uncertain significance Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant 2022-10-07 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1408 of the FLNC protein (p.Glu1408Lys). This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. ClinVar contains an entry for this variant (Variation ID: 856144). 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.
Athena Diagnostics RCV001288180 SCV001475124 uncertain significance not provided 2020-03-19 criteria provided, single submitter clinical testing
GeneDx RCV001288180 SCV001791166 uncertain significance not provided 2023-09-19 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Ambry Genetics RCV002327335 SCV002630111 uncertain significance Cardiovascular phenotype 2022-09-22 criteria provided, single submitter clinical testing The p.E1408K variant (also known as c.4222G>A), located in coding exon 24 of the FLNC gene, results from a G to A substitution at nucleotide position 4222. The glutamic acid at codon 1408 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV001288180 SCV003833133 uncertain significance not provided 2020-02-28 criteria provided, single submitter clinical testing

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