ClinVar Miner

Submissions for variant NM_001458.4(FLNC):c.1166G>A (p.Gly389Asp) (rs763039506)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000487193 SCV000565014 uncertain significance not provided 2020-12-22 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 418214; Landrum et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Invitae RCV000649173 SCV000770998 uncertain significance Myofibrillar myopathy, filamin C-related; Myopathy, distal, 4; Cardiomyopathy, familial hypertrophic, 26; Dilated Cardiomyopathy, Dominant 2020-10-09 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 389 of the FLNC protein (p.Gly389Asp). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs763039506, ExAC 0.05%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with FLNC-related disease. ClinVar contains an entry for this variant (Variation ID: 418214). 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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000487193 SCV001739723 uncertain significance not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000487193 SCV001929540 uncertain significance not provided no assertion criteria provided clinical testing

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