Submissions for variant NM_001458.5(FLNC):c.5704del (p.Ala1902fs)

dbSNP: rs1554400703

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000498963	SCV000590072	pathogenic	not provided	2017-05-31	criteria provided, single submitter	clinical testing	The c.5704delG variant in the FLNC gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.5704delG variant causes a frameshift starting with codon Alanine 1902, changes this amino acid to a Glutamine residue, and creates a premature Stop codon at position 51 of the new reading frame, denoted p.Ala1902GlnfsX51. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.5704delG variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.5704delG as a pathogenic variant.
Invitae	RCV003766797	SCV004607171	pathogenic	Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant	2024-01-24	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ala1902Glnfs*51) in the FLNC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FLNC are known to be pathogenic (PMID: 27908349). This variant is not present in population databases (gnomAD no frequency). 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: 432355). For these reasons, this variant has been classified as Pathogenic.