ClinVar Miner

Submissions for variant NM_001458.5(FLNC):c.3745G>A (p.Asp1249Asn)

gnomAD frequency: 0.00001  dbSNP: rs774968828
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000649135 SCV000770960 uncertain significance Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant 2023-10-14 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1249 of the FLNC protein (p.Asp1249Asn). This variant is present in population databases (rs774968828, 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: 539405). 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.
Ambry Genetics RCV002343337 SCV002622678 uncertain significance Cardiovascular phenotype 2021-06-12 criteria provided, single submitter clinical testing The p.D1249N variant (also known as c.3745G>A), located in coding exon 21 of the FLNC gene, results from a G to A substitution at nucleotide position 3745. The aspartic acid at codon 1249 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is conserved. 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.
Revvity Omics, Revvity RCV003144440 SCV003833606 uncertain significance not provided 2022-09-14 criteria provided, single submitter clinical testing

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