ClinVar Miner

Submissions for variant NM_001458.4(FLNC):c.1444C>T (p.Arg482Ter) (rs1420159591)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000615997 SCV000731357 uncertain significance not specified 2016-12-07 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The p.Arg482X v ariant in FLNC has not been previously reported in individuals with cardiomyopat hy but has been identified by our laboratory in 1 individual with DCM and segreg ated with disease in at least 1 affected relative. It was absent from large popu lation studies. This nonsense variant leads to a premature termination codon at position 482, which is predicted to lead to a truncated or absent protein. The F LNC gene is associated with myofibrillar myopathy but variants have recently als o been reported in individuals with isolated inherited cardiomyopathies (includi ng HCM, DCM and RCM). Overall the number of reported variants is still low and l oss of function as a disease mechanism is not yet firmly established for this ge ne. In summary, while there is some suspicion for a pathogenic role, the clinica l significance of the p.Arg482X variant is uncertain.
Invitae RCV000701881 SCV000830704 pathogenic Myofibrillar myopathy, filamin C-related; Myopathy, distal, 4; Cardiomyopathy, familial hypertrophic, 26; Dilated Cardiomyopathy, Dominant 2018-06-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg482*) in the FLNC gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FLNC-related disease. ClinVar contains an entry for this variant (Variation ID: 517207). Loss-of-function variants in FLNC are known to be pathogenic (PMID: 27908349). For these reasons, this variant has been classified as Pathogenic.

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