Submissions for variant NM_001458.5(FLNC):c.4134G>A (p.Ala1378=)

gnomAD frequency: 0.00001  dbSNP: rs200942470

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Phosphorus, Inc.	RCV001823751	SCV002073453	likely benign	not specified	2022-01-18	criteria provided, single submitter	clinical testing	This synonymous variant has an entry in ClinVar (810192) NM_001458.5 (FLNC): c.4134G>A (p.Ala1378=) and has occurred in GnomAD with a total MAF of 0.0029% and highest MAF of 0.0116% in the East Asian population. This position is not conserved. In silico splicing algorithm was unavailable, however it is not predicted to impact splicing due to its distance from the splice site. No functional studies were performed to confirm this prediction. The variant has not occurred in literature associated with disease. Considering the above evidence, this variant has been classified as Likely Benign.
Invitae	RCV002068739	SCV002399947	likely benign	Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant	2023-12-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002327227	SCV002629343	likely benign	Cardiovascular phenotype	2019-11-01	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.
PreventionGenetics, part of Exact Sciences	RCV003953415	SCV004782154	likely benign	FLNC-related disorder	2022-01-25	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).
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000998919	SCV001952135	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000998919	SCV001971425	likely benign	not provided		no assertion criteria provided	clinical testing