ClinVar Miner

Submissions for variant NM_001458.4(FLNC):c.4991C>T (p.Thr1664Met) (rs780829334)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000585445 SCV000590283 uncertain significance not provided 2019-04-30 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 31918855)
CeGaT Praxis fuer Humangenetik Tuebingen RCV000585445 SCV000693254 uncertain significance not provided 2017-08-01 criteria provided, single submitter clinical testing
Invitae RCV000649125 SCV000770950 uncertain significance Myofibrillar myopathy, filamin C-related; Myopathy, distal, 4; Cardiomyopathy, familial hypertrophic, 26; Dilated Cardiomyopathy, Dominant 2020-10-12 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 1664 of the FLNC protein (p.Thr1664Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs780829334, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in individual(s) with left ventricular noncompaction cardiomyopathy (LVNC) (PMID: 31918855). ClinVar contains an entry for this variant (Variation ID: 432545). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or 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.
Institute of Human Genetics, University of Leipzig Medical Center RCV001262958 SCV001441017 uncertain significance Cardiomyopathy, familial hypertrophic, 26 2019-01-01 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000585445 SCV001714857 uncertain significance not provided 2020-08-14 criteria provided, single submitter clinical testing

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