Submissions for variant NM_001458.5(FLNC):c.2811+5G>A

gnomAD frequency: 0.00001  dbSNP: rs781538211

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001294391	SCV001483268	uncertain significance	Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant	2023-05-23	criteria provided, single submitter	clinical testing	Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 998523). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This variant is present in population databases (rs781538211, gnomAD 0.02%). This sequence change falls in intron 18 of the FLNC gene. It does not directly change the encoded amino acid sequence of the FLNC protein. It affects a nucleotide within the consensus splice site. 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	RCV001751556	SCV001995327	uncertain significance	not provided	2019-12-06	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.
New York Genome Center	RCV001839040	SCV002099335	uncertain significance	Hypertrophic cardiomyopathy 26	2021-04-23	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002437000	SCV002752333	uncertain significance	Cardiovascular phenotype	2020-12-01	criteria provided, single submitter	clinical testing	The c.2811+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 18 in the FLNC gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.