Submissions for variant NM_001267550.2(TTN):c.73303C>T (p.Arg24435Cys)

gnomAD frequency: 0.00012  dbSNP: rs200028088

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001704918	SCV000237523	likely benign	not provided	2018-10-12	criteria provided, single submitter	clinical testing
Invitae	RCV000643177	SCV000764864	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-11-02	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000184805	SCV001157846	uncertain significance	not specified	2018-09-26	criteria provided, single submitter	clinical testing	The TTN c.65599C>T; p.Arg21867Cys variant (rs200028088; ClinVar Variation ID: 202847) is rare in the general population (<1% allele frequency in the Genome Aggregation Database) and has not been reported in the medical literature in association with dilated cardiomyopathy (DCM) or other TTN-related disease. The clinical relevance of rare missense variants in this gene, which are identified on average once per individual sequenced in affected populations (Herman 2012), is not well understood. Yet, evidence suggests that the vast majority of such missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Thus, the clinical significance of the p.Arg21867Cys variant cannot be determined with certainty.
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001197045	SCV001367680	uncertain significance	See cases	2020-03-17	criteria provided, single submitter	clinical testing	This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2,PP3.
Ambry Genetics	RCV002336483	SCV002637763	uncertain significance	Cardiovascular phenotype	2018-01-16	criteria provided, single submitter	clinical testing	The p.R15370C variant (also known as c.46108C>T), located in coding exon 153 of the TTN gene, results from a C to T substitution at nucleotide position 46108. The arginine at codon 15370 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV001704918	SCV003818431	uncertain significance	not provided	2023-08-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001704918	SCV004150290	uncertain significance	not provided	2022-11-01	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV001704918	SCV004225817	uncertain significance	not provided	2023-05-17	criteria provided, single submitter	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001704918	SCV001979648	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001704918	SCV001980483	uncertain significance	not provided		no assertion criteria provided	clinical testing