ClinVar Miner

Submissions for variant NM_001458.4(FLNC):c.6572C>T (p.Thr2191Met) (rs768329311)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482064 SCV000573597 uncertain significance not provided 2018-07-10 criteria provided, single submitter clinical testing The T2191M variant in the FLNC gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The T2191M variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The T2191M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret T2191M as a variant of uncertain significance.
Invitae RCV000689890 SCV000817560 uncertain significance Myofibrillar myopathy, filamin C-related; Myopathy, distal, 4; Cardiomyopathy, familial hypertrophic, 26; Dilated Cardiomyopathy, Dominant 2019-12-12 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 2191 of the FLNC protein (p.Thr2191Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs768329311, ExAC 0.04%). This variant has not been reported in the literature in individuals with FLNC-related disease. ClinVar contains an entry for this variant (Variation ID: 423849). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.