Submissions for variant NM_001458.5(FLNC):c.1948C>T (p.Arg650Ter)

dbSNP: rs770606675

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000479811	SCV000570342	pathogenic	not provided	2023-05-15	criteria provided, single submitter	clinical testing	Has been reported in association with DCM in published literature (Morales et al., 2020) and in an individual tested at GeneDx; Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26899768, 15929027, 32112656, 32160020, 36472615)
Invitae	RCV000552507	SCV000659715	pathogenic	Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant	2023-08-28	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg650*) 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: 421215). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV002413329	SCV002722260	pathogenic	Cardiovascular phenotype	2019-06-19	criteria provided, single submitter	clinical testing	The p.R650* variant (also known as c.1948C>T), located in coding exon 12 of the FLNC gene, results from a C to T substitution at nucleotide position 1948. This changes the amino acid from an arginine to a stop codon within coding exon 12. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000479811	SCV001744741	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000479811	SCV001924043	pathogenic	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000479811	SCV001928382	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000479811	SCV001966427	likely pathogenic	not provided		no assertion criteria provided	clinical testing