Submissions for variant NM_001458.5(FLNC):c.7841_7842del (p.Val2614fs)

dbSNP: rs1554402003

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000797152	SCV000936695	pathogenic	Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant	2022-11-07	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the FLNC protein in which other variant(s) (p.Trp2710*) have been determined to be pathogenic (PMID: 15929027, 22961544, 26472074, 26969713). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 643452). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val2614Aspfs*66) in the FLNC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 112 amino acid(s) of the FLNC protein.
Revvity Omics, Revvity	RCV003141783	SCV003828144	likely pathogenic	not provided	2022-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV003141783	SCV004170370	likely pathogenic	not provided	2023-10-06	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation, as the last 112 amino acids are replaced with 65 different amino acids, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
GenomeConnect - Invitae Patient Insights Network	RCV001535530	SCV001749500	not provided	Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 11-26-2018 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.