ClinVar Miner

Submissions for variant NM_001458.4(FLNC):c.7560C>T (p.Thr2520=) (rs527921534)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000547791 SCV000651170 uncertain significance Myofibrillar myopathy, filamin C-related; Myopathy, distal, 4; Cardiomyopathy, familial hypertrophic, 26; Dilated Cardiomyopathy, Dominant 2018-06-17 criteria provided, single submitter clinical testing This sequence change affects codon 2520 of the FLNC mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the FLNC protein. This variant is present in population databases (rs527921534, ExAC 0.04%). This variant has not been reported in the literature in individuals with FLNC-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, 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.
Stanford Center for Inherited Cardiovascular Disease,Stanford University RCV000786412 SCV000925230 uncertain significance not provided 2017-09-11 no assertion criteria provided provider interpretation c.7560C>T (silent, splice region) in exon 45 of the FLNC gene (NM_001458.4; chr7-128496974-C-T) SCICD classification: variant of uncertain significance based on lack of case data. However, this variant is relatively prevalent in some ethnic populations. We do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). Gene-level evidence: Both missense and truncating variants in FLNC have been reported in various cardiomyopathies (Ortiz-Genga et al. 2016; Valdes-Mas et al 2014). Variant type: Missense. Case data: · ClinVar: not present · Cases in the literature: none reported Functional data: none reported. In silico models (for missense variants only): not applicable Splicing algorithms: Per the test report, "Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies." Conservation data: The thymine at position 7560 in the cDNA is completely conserved across species, as are neighboring nucleotides. Other variants associated with disease at this nucleotide: none Population data: MAF=0.02% in East Asians: · The variant was reported online in 8 of 137,599 individuals in the Genome Aggregation Consortium Dataset (gnomAD; http://gnomad.broadinstitute.org/), which currently includes variant calls on >140,000 unrelated individuals of African, Asian, European, Ashkenazi, Latino descent. Specifically, the variant was observed in 4 of 9,414 individuals of East Asian descent (MAF=0.02%), 3 of 15,367 individuals of South Asian descent and 1 of 62,589 individuals of European descent. The phenotype of those individuals is not publicly available. The dataset is comprised of multiple cohorts, some of which were recruited from the general population, others were enriched for common cardiovascular disease.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.