Submissions for variant NM_001103.4(ACTN2):c.1192C>T (p.Arg398Cys)

gnomAD frequency: 0.00010  dbSNP: rs148189507

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000537863	SCV000636929	benign	Dilated cardiomyopathy 1AA; Primary familial hypertrophic cardiomyopathy	2024-12-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001700404	SCV002073973	uncertain significance	not provided	2022-01-25	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 463190)
Ambry Genetics	RCV002350237	SCV002646034	uncertain significance	Cardiovascular phenotype	2024-07-02	criteria provided, single submitter	clinical testing	The p.R398C variant (also known as c.1192C>T), located in coding exon 11 of the ACTN2 gene, results from a C to T substitution at nucleotide position 1192. The arginine at codon 398 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant was detected in a cardiomyopathy genetic testing cohort as well as a dilated cardiomyopathy cohort; however, clinical details were limited, and additional cardiac variants were detected in some cases. (van Lint FHM et al, 2019 Jun;27:304-309; Horvat C et al. Genet. Med., 2019 01;21:133-143). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000604601	SCV000733999	uncertain significance	Dilated cardiomyopathy 1AA		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001700404	SCV001924505	uncertain significance	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001700404	SCV001931804	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001700404	SCV001956140	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001700404	SCV001973377	uncertain significance	not provided		no assertion criteria provided	clinical testing