ClinVar Miner

Submissions for variant NM_001458.5(FLNC):c.4109G>A (p.Arg1370Gln)

gnomAD frequency: 0.00001  dbSNP: rs761881020
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000788573 SCV000927728 uncertain significance not provided 2018-06-06 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001065013 SCV001229951 uncertain significance Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant 2024-10-01 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1370 of the FLNC protein (p.Arg1370Gln). This variant is present in population databases (rs761881020, gnomAD 0.002%). This missense change has been observed in individual(s) with frontotemporaldementia (PMID: 26555887). ClinVar contains an entry for this variant (Variation ID: 636671). Invitae Evidence 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 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 RCV000788573 SCV002504267 likely benign not provided 2020-02-07 criteria provided, single submitter clinical testing See Variant Classification Assertion Criteria.
Ambry Genetics RCV002325491 SCV002626912 uncertain significance Cardiovascular phenotype 2024-07-31 criteria provided, single submitter clinical testing The p.R1370Q variant (also known as c.4109G>A), located in coding exon 23 of the FLNC gene, results from a G to A substitution at nucleotide position 4109. The arginine at codon 1370 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been reported in a frontotemporal dementia cohort (Janssens J et al. Acta Neuropathol Commun, 2015 Nov;3:68). 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. Based on the available evidence, the clinical significance of this variant remains unclear.

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