Submissions for variant NM_001267550.2(TTN):c.52852C>T (p.Arg17618Cys)

gnomAD frequency: 0.00115  dbSNP: rs201213901

Total submissions: 24

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000118765	SCV000051490	likely benign	not provided	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000040336	SCV000064027	uncertain significance	not specified	2015-05-21	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Arg15050Cys v ariant in TTN has been previously identified by our laboratory in 1 adult with D CM, who carried a likely pathogenic variant in another gene, and in 1 adult with HCM. This variant has been identified in 0.2% (146/66698) of European chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs201213901). Computational prediction tools and conservation analysis sugge st that this variant may impact the protein, though this information is not pred ictive enough to determine pathogenicity. In summary, while the clinical signifi cance of the p.Arg15050Cys variant is uncertain, its frequency in the general po pulation suggests that it is more likely to be benign.
Genetic Services Laboratory, University of Chicago	RCV000118765	SCV000153297	uncertain significance	not provided	2013-10-08	criteria provided, single submitter	clinical testing
Invitae	RCV001084228	SCV000555523	likely benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-29	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000118765	SCV000700961	uncertain significance	not provided	2018-06-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000118765	SCV000730383	likely benign	not provided	2021-01-08	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000118765	SCV000884775	uncertain significance	not provided	2023-11-29	criteria provided, single submitter	clinical testing	The TTN c.45148C>T; p.Arg15050Cys variant is rare in the general population (<1% allele frequency in the Genome Aggregation Database) and have 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. While the clinical significance of such variants is considered uncertain, evidence suggests that the vast majority of missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Given the available evidence, the clinical significance of the c.45148C>T; p.Arg15050Cys variant cannot be determined with certainty.
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852845	SCV000995576	likely benign	Primary dilated cardiomyopathy; Cardiomyopathy	2019-05-14	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000118765	SCV001152880	likely benign	not provided	2023-02-01	criteria provided, single submitter	clinical testing	TTN: BS2
Illumina Laboratory Services, Illumina	RCV001129508	SCV001289041	uncertain significance	Dilated cardiomyopathy 1G	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001129509	SCV001289042	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001129510	SCV001289043	uncertain significance	Early-onset myopathy with fatal cardiomyopathy	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001129511	SCV001289044	benign	Tibial muscular dystrophy	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001136507	SCV001296346	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Athena Diagnostics	RCV000040336	SCV001879658	benign	not specified	2020-10-19	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798159	SCV002042535	benign	Cardiomyopathy	2020-07-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002426577	SCV002740248	likely benign	Cardiovascular phenotype	2019-03-28	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.
Revvity Omics, Revvity	RCV000118765	SCV003819794	uncertain significance	not provided	2023-04-24	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004534905	SCV004747672	likely benign	TTN-related disorder	2022-04-03	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).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000118765	SCV001743679	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000040336	SCV001923367	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000118765	SCV001931237	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000118765	SCV001952836	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000118765	SCV001964926	likely benign	not provided		no assertion criteria provided	clinical testing