Submissions for variant NM_001458.5(FLNC):c.5272C>T (p.Arg1758Trp)

gnomAD frequency: 0.00001  dbSNP: rs369187211

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000691370	SCV000819146	likely benign	Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant	2023-11-09	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000764686	SCV000895818	uncertain significance	Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26	2018-10-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001547864	SCV001767664	likely benign	not provided	2021-01-18	criteria provided, single submitter	clinical testing	Reported in one adult patient with sporadic frontotemporal dementia (Janssens et al., 2015); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID#570505; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 26555887)
Ambry Genetics	RCV002343461	SCV002646559	uncertain significance	Cardiovascular phenotype	2022-10-19	criteria provided, single submitter	clinical testing	The p.R1758W variant (also known as c.5272C>T), located in coding exon 31 of the FLNC gene, results from a C to T substitution at nucleotide position 5272. The arginine at codon 1758 is replaced by tryptophan, an amino acid with dissimilar properties. This variant has been detected in a frontotemporal dementia cohort (Janssens J et al. Acta Neuropathol Commun, 2015 Nov;3:68). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003150332	SCV003837902	uncertain significance	Cardiomyopathy	2022-04-06	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001547864	SCV004161042	likely benign	not provided	2023-02-01	criteria provided, single submitter	clinical testing	FLNC: BS2
Revvity Omics, Revvity	RCV001547864	SCV004234806	uncertain significance	not provided	2023-05-11	criteria provided, single submitter	clinical testing