Submissions for variant NM_001458.5(FLNC):c.4553A>G (p.Lys1518Arg)

gnomAD frequency: 0.00061  dbSNP: rs201635205

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000176640	SCV000228329	uncertain significance	not provided	2014-10-27	criteria provided, single submitter	clinical testing
Invitae	RCV001088530	SCV000771082	likely benign	Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant	2024-01-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000176640	SCV001832618	benign	not provided	2021-06-22	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26582918)
Ambry Genetics	RCV002326965	SCV002634225	likely benign	Cardiovascular phenotype	2019-04-19	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003150050	SCV003837900	benign	Cardiomyopathy	2022-05-13	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224192	SCV003919979	uncertain significance	Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26	2021-03-30	criteria provided, single submitter	clinical testing	FLNC NM_001458.4 exon 26 p.Lys1518Arg (c.4553A>G): This variant has not been reported in the literature but is present in 0.1% (44/22636) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/7-128488095-A-G). This variant is present in ClinVar (Variation ID:195949). Evolutionary conservation suggests that this variant may impact the protein; computational predictive tools suggest that this variant may not impact the protein. Of note, computational tools designed to predict splicing suggest a potential effect from this variant. However, further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
PreventionGenetics, part of Exact Sciences	RCV003965275	SCV004782099	likely benign	FLNC-related disorder	2023-05-22	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Clinical Genetics, Academic Medical Center	RCV000176640	SCV001921040	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000176640	SCV001968488	likely benign	not provided		no assertion criteria provided	clinical testing