Submissions for variant NM_001458.5(FLNC):c.6826G>A (p.Val2276Met)

dbSNP: rs1207179287

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001243535	SCV001416703	uncertain significance	Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant	2023-09-27	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 968410). 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) performed at Invitae indicates that this missense variant is not expected to disrupt 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. This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 2276 of the FLNC protein (p.Val2276Met). This variant is not present in population databases (gnomAD no frequency).
GeneDx	RCV001537610	SCV001754509	uncertain significance	not provided	2021-03-17	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
CeGaT Center for Human Genetics Tuebingen	RCV001537610	SCV002586197	uncertain significance	not provided	2022-08-01	criteria provided, single submitter	clinical testing	FLNC: PM2
Ambry Genetics	RCV002366073	SCV002665238	uncertain significance	Cardiovascular phenotype	2023-11-21	criteria provided, single submitter	clinical testing	The p.V2276M variant (also known as c.6826G>A), located in coding exon 41 of the FLNC gene, results from a G to A substitution at nucleotide position 6826. The valine at codon 2276 is replaced by methionine, 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.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV003989654	SCV004806563	uncertain significance	Hypertrophic cardiomyopathy 26	2024-03-26	criteria provided, single submitter	clinical testing