Submissions for variant NM_001458.5(FLNC):c.2642-2dup

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV003788910	SCV004571772	uncertain significance	Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant	2022-12-17	criteria provided, single submitter	clinical testing	Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies and prediction algorithms are not available or were not evaluated, and the effect of this variant on mRNA splicing is currently unknown. This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change falls in intron 17 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.
Ambry Genetics	RCV004366541	SCV005017727	uncertain significance	Cardiovascular phenotype	2023-12-07	criteria provided, single submitter	clinical testing	The c.2642-2dupA intronic variant is located 2 nucleotides before coding exon 18 in the FLNC gene. This variant results from a duplication of 1 nucleotide at position c.2642-2. This variant does not change the sequence of the canonical acceptor at this splice site. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.