ClinVar Miner

Submissions for variant NM_001458.4(FLNC):c.7382G>A (p.Ser2461Asn) (rs550547714)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000267784 SCV000334368 uncertain significance not provided 2015-08-25 criteria provided, single submitter clinical testing
Invitae RCV000699663 SCV000828385 uncertain significance Myofibrillar myopathy, filamin C-related; Myopathy, distal, 4; Cardiomyopathy, familial hypertrophic, 26; Dilated Cardiomyopathy, Dominant 2018-04-09 criteria provided, single submitter clinical testing This sequence change replaces serine with asparagine at codon 2461 of the FLNC protein (p.Ser2461Asn). The serine residue is highly conserved and there is a small physicochemical difference between serine and asparagine. This variant is present in population databases (rs550547714, ExAC 0.005%). This variant has been reported in an individual affected with frontotemporal dementia (PMID: 26555887). ClinVar contains an entry for this variant (Variation ID: 282755). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV000267784 SCV001816213 uncertain significance not provided 2019-09-11 criteria provided, single submitter clinical testing Has not been previously reported in association with FLNC-related disease to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 282755; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31127727, 26555887)
Clinical Genetics,Academic Medical Center RCV000267784 SCV001919554 uncertain significance not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000267784 SCV001929813 uncertain significance not provided no assertion criteria provided clinical testing

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