ClinVar Miner

Submissions for variant NM_001458.4(FLNC):c.2296C>T (p.Arg766Trp) (rs200215340)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000534354 SCV000650940 uncertain significance Myofibrillar myopathy, filamin C-related; Myopathy, distal, 4; Cardiomyopathy, familial hypertrophic, 26; Dilated Cardiomyopathy, Dominant 2020-09-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 766 of the FLNC protein (p.Arg766Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs200215340, ExAC 0.05%). This variant has not been reported in the literature in individuals with FLNC-related conditions. ClinVar contains an entry for this variant (Variation ID: 472004). 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). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
GeneDx RCV001564850 SCV001788078 uncertain significance not provided 2021-05-14 criteria provided, single submitter clinical testing Reported in a patient with a history of sudden cardiac arrest in the published literature (Cohen et al., 2021); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 472004; Landrum et al., 2016) This variant is associated with the following publications: (PMID: 33652119)

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