Submissions for variant NM_001458.5(FLNC):c.5579G>A (p.Arg1860His)

gnomAD frequency: 0.00002  dbSNP: rs1019973830

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000484170	SCV000573449	uncertain significance	not provided	2018-11-07	criteria provided, single submitter	clinical testing	The R1860H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R1860H variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Invitae	RCV000649140	SCV000770965	likely benign	Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant	2023-11-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002350077	SCV002650937	uncertain significance	Cardiovascular phenotype	2023-09-11	criteria provided, single submitter	clinical testing	The p.R1860H variant (also known as c.5579G>A), located in coding exon 34 of the FLNC gene, results from a G to A substitution at nucleotide position 5579. The arginine at codon 1860 is replaced by histidine, an amino acid with highly similar 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.