Submissions for variant NM_001458.5(FLNC):c.4420C>T (p.Arg1474Trp)

gnomAD frequency: 0.00003  dbSNP: rs372454458

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000522249	SCV000621851	uncertain significance	not provided	2017-10-27	criteria provided, single submitter	clinical testing	The R1474W variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R1474W variant is observed in 1/9,826 (0.01%) alleles from individuals of Ashkenazi Jewish background (Lek et al., 2016). This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Invitae	RCV000705455	SCV000834453	likely benign	Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant	2023-11-22	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000522249	SCV001155272	uncertain significance	not provided	2016-05-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002329244	SCV002628125	uncertain significance	Cardiovascular phenotype	2021-03-02	criteria provided, single submitter	clinical testing	The p.R1474W variant (also known as c.4420C>T), located in coding exon 25 of the FLNC gene, results from a C to T substitution at nucleotide position 4420. The arginine at codon 1474 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is not 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.
Revvity Omics, Revvity	RCV000522249	SCV004234804	uncertain significance	not provided	2023-07-17	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003486857	SCV004240650	uncertain significance	Cardiomyopathy	2023-05-03	criteria provided, single submitter	clinical testing