ClinVar Miner

Submissions for variant NM_001458.5(FLNC):c.2602A>G (p.Ser868Gly)

gnomAD frequency: 0.00008  dbSNP: rs201002262
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000804911 SCV000944849 uncertain significance Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant 2024-01-06 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 868 of the FLNC protein (p.Ser868Gly). This variant is present in population databases (rs201002262, gnomAD 0.01%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with FLNC-related conditions. ClinVar contains an entry for this variant (Variation ID: 649876). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FLNC protein function. 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 RCV001731934 SCV001983340 uncertain significance not provided 2023-09-01 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Ambry Genetics RCV002424868 SCV002744478 uncertain significance Cardiovascular phenotype 2022-01-07 criteria provided, single submitter clinical testing The p.S868G variant (also known as c.2602A>G), located in coding exon 17 of the FLNC gene, results from an A to G substitution at nucleotide position 2602. The serine at codon 868 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002495095 SCV002787622 uncertain significance Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26 2021-10-11 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001731934 SCV003833150 uncertain significance not provided 2020-07-29 criteria provided, single submitter clinical testing

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