Submissions for variant NM_001103.4(ACTN2):c.1298C>T (p.Ser433Leu)

gnomAD frequency: 0.00068  dbSNP: rs143749154

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154651	SCV000204326	benign	not specified	2013-10-10	criteria provided, single submitter	clinical testing	Ser433Leu in Exon 12 of ACTN2: This variant is not expected to have clinical sig nificance because it has been identified in 1.0% (46/4406) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs143749154).
GeneDx	RCV000154651	SCV000235666	benign	not specified	2016-10-27	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV001082455	SCV000285856	benign	Dilated cardiomyopathy 1AA; Primary familial hypertrophic cardiomyopathy	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000251654	SCV000317746	benign	Cardiovascular phenotype	2018-02-27	criteria provided, single submitter	clinical testing	This alteration is classified as 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	RCV000768738	SCV000900108	benign	Cardiomyopathy	2023-06-08	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000845357	SCV000987411	likely benign	not provided		criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004551337	SCV004746474	benign	ACTN2-related disorder	2019-05-10	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000845357	SCV001742926	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000154651	SCV001917399	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000154651	SCV001966666	benign	not specified		no assertion criteria provided	clinical testing