Submissions for variant NM_001458.5(FLNC):c.3209C>T (p.Pro1070Leu)

gnomAD frequency: 0.00005  dbSNP: rs370391049

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000649094	SCV000770919	likely benign	Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant	2024-01-04	criteria provided, single submitter	clinical testing
GeneDx	RCV001756082	SCV001997523	uncertain significance	not provided	2023-05-19	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Ambry Genetics	RCV002325296	SCV002609338	uncertain significance	Cardiovascular phenotype	2023-10-24	criteria provided, single submitter	clinical testing	The p.P1070L variant (also known as c.3209C>T), located in coding exon 21 of the FLNC gene, results from a C to T substitution at nucleotide position 3209. The proline at codon 1070 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV001756082	SCV003831459	uncertain significance	not provided	2021-10-12	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003420137	SCV004113792	uncertain significance	FLNC-related disorder	2023-03-28	criteria provided, single submitter	clinical testing	The FLNC c.3209C>T variant is predicted to result in the amino acid substitution p.Pro1070Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-128484728-C-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003486910	SCV004240639	uncertain significance	Cardiomyopathy	2023-05-16	criteria provided, single submitter	clinical testing