ClinVar Miner

Submissions for variant NM_001458.5(FLNC):c.7486G>T (p.Val2496Phe)

dbSNP: rs200295337
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000785096 SCV000923653 uncertain significance not specified 2019-01-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV002388412 SCV002668600 uncertain significance Cardiovascular phenotype 2023-05-11 criteria provided, single submitter clinical testing The p.V2496F variant (also known as c.7486G>T), located in coding exon 45 of the FLNC gene, results from a G to T substitution at nucleotide position 7486. The valine at codon 2496 is replaced by phenylalanine, an amino acid with highly 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.
Invitae RCV002535719 SCV003470831 uncertain significance Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant 2023-11-13 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 2496 of the FLNC protein (p.Val2496Phe). This variant is present in population databases (rs200295337, gnomAD 0.002%). 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: 634579). 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) performed at Invitae indicates that this missense variant is not expected to disrupt FLNC protein function with a negative predictive value of 80%. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.