Submissions for variant NM_001458.5(FLNC):c.3295G>A (p.Val1099Ile)

gnomAD frequency: 0.00002  dbSNP: rs759452636

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000487754	SCV000575535	uncertain significance	not provided	2016-09-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000487754	SCV000619958	likely benign	not provided	2021-11-12	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function
Invitae	RCV001368325	SCV001564716	uncertain significance	Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant	2023-12-27	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1099 of the FLNC protein (p.Val1099Ile). This variant is present in population databases (rs759452636, gnomAD 0.007%). 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: 425426). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FLNC protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV002323848	SCV002611178	uncertain significance	Cardiovascular phenotype	2020-01-15	criteria provided, single submitter	clinical testing	The p.V1099I variant (also known as c.3295G>A), located in coding exon 21 of the FLNC gene, results from a G to A substitution at nucleotide position 3295. The valine at codon 1099 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV000487754	SCV003833611	uncertain significance	not provided	2023-02-03	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003150239	SCV003837896	uncertain significance	Cardiomyopathy	2022-05-19	criteria provided, single submitter	clinical testing