Submissions for variant NM_001458.5(FLNC):c.1924G>A (p.Val642Ile)

gnomAD frequency: 0.00019  dbSNP: rs369387744

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000525252	SCV000650925	likely benign	Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant	2023-12-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001546268	SCV001765760	likely benign	not provided	2021-05-05	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 471991; Landrum et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001824825	SCV002074338	uncertain significance	not specified	2022-01-19	criteria provided, single submitter	clinical testing	Variant summary: FLNC c.1924G>A (p.Val642Ile) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-05 in 249578 control chromosomes, predominantly at a frequency of 0.00032 within the African or African-American subpopulation in the gnomAD database. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1924G>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics	RCV002413599	SCV002721517	uncertain significance	Cardiovascular phenotype	2022-07-20	criteria provided, single submitter	clinical testing	The p.V642I variant (also known as c.1924G>A), located in coding exon 12 of the FLNC gene, results from a G to A substitution at nucleotide position 1924. The valine at codon 642 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is 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	RCV001546268	SCV003833037	uncertain significance	not provided	2020-11-17	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001546268	SCV001807415	uncertain significance	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001546268	SCV001927442	uncertain significance	not provided		no assertion criteria provided	clinical testing