Submissions for variant NM_001458.5(FLNC):c.2068T>C (p.Phe690Leu)

gnomAD frequency: 0.00023  dbSNP: rs200943714

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000649153	SCV000770978	likely benign	Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant	2025-01-20	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV001171871	SCV001714853	uncertain significance	not provided	2020-02-21	criteria provided, single submitter	clinical testing
GeneDx	RCV001171871	SCV001788611	likely benign	not provided	2020-11-25	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 539419; Landrum et al., 2016)
Ambry Genetics	RCV002422377	SCV002725658	uncertain significance	Cardiovascular phenotype	2024-10-11	criteria provided, single submitter	clinical testing	The p.F690L variant (also known as c.2068T>C), located in coding exon 13 of the FLNC gene, results from a T to C substitution at nucleotide position 2068. The phenylalanine at codon 690 is replaced by leucine, an amino acid with highly similar properties. This variant has been reported in a hypertrophic cardiomyopathy (HCM) cohort, but clinical details were limited (Bonaventura J et al. J Am Heart Assoc, 2024 May;13:e033565). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Revvity Omics, Revvity	RCV001171871	SCV003833044	uncertain significance	not provided	2021-05-21	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003486911	SCV004240620	uncertain significance	Cardiomyopathy	2023-05-16	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001171871	SCV005875517	uncertain significance	not provided	2024-06-04	criteria provided, single submitter	clinical testing	The FLNC c.2068T>C; p.Phe690Leu variant (rs200943714), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 539419). This variant is found in the non-Finnish European population with an allele frequency of 0.03% (44/128,716 alleles) in the Genome Aggregation Database (v2.1.1). Computational analyses predict that this variant is deleterious (REVEL: 0.88). However, given the lack of clinical and functional data, the significance of this variant is uncertain at this time.
Clinical Genetics, Academic Medical Center	RCV001171871	SCV001925634	uncertain significance	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001171871	SCV001962863	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001171871	SCV002038186	uncertain significance	not provided		no assertion criteria provided	clinical testing