Submissions for variant NM_001267550.2(TTN):c.52853G>A (p.Arg17618His)

gnomAD frequency: 0.00016  dbSNP: rs371538664

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000222321	SCV000272682	uncertain significance	not specified	2015-06-09	criteria provided, single submitter	clinical testing	The p.Arg15050His variant in TTN has not been reported in individuals with cardi omyopathy, but has been identified in 23/66697 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs371538664 ). Computational prediction tools and conservation analysis suggest that this va riant may impact the protein, though this information is not predictive enough t o determine pathogenicity. In summary, the clinical significance of the p.Arg150 50His variant is uncertain.
Invitae	RCV000550187	SCV000643327	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-12-15	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000997454	SCV001152879	uncertain significance	not provided	2023-10-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001136502	SCV001296341	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	RCV001136503	SCV001296342	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2017-11-07	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	RCV001136504	SCV001296343	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	RCV001136505	SCV001296344	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	RCV001136506	SCV001296345	benign	Tibial muscular dystrophy	2017-11-07	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.
GeneDx	RCV000997454	SCV001790876	likely benign	not provided	2021-04-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002429076	SCV002741195	likely benign	Cardiovascular phenotype	2019-08-26	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.