Submissions for variant NM_001267550.2(TTN):c.63917G>A (p.Arg21306His)

gnomAD frequency: 0.00010  dbSNP: rs202240487

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000172287	SCV000051293	uncertain significance	not provided	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000040471	SCV000064162	benign	not specified	2014-11-20	criteria provided, single submitter	clinical testing	p.Arg18738His in exon 256 of TTN: This variant is not expected to have clinical significance because it has been identified in 1.4% (229/16568) of South Asian c hromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute .org; dbSNP rs202240487).
GeneDx	RCV000040471	SCV000237409	benign	not specified	2018-01-15	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.
Genetic Services Laboratory, University of Chicago	RCV000040471	SCV000249276	likely benign	not specified	2015-04-04	criteria provided, single submitter	clinical testing
Invitae	RCV001086239	SCV000643511	benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-04	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001130765	SCV001290355	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2017-08-18	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	RCV001130766	SCV001290356	likely benign	Dilated cardiomyopathy 1G	2017-08-18	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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV001130767	SCV001290357	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	RCV001130768	SCV001290358	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	RCV001130769	SCV001290359	benign	Tibial muscular dystrophy	2017-08-18	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001170812	SCV001333430	benign	Cardiomyopathy	2017-11-02	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000040471	SCV001476350	benign	not specified	2019-09-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002453331	SCV002614104	benign	Cardiovascular phenotype	2020-09-03	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: 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.
CeGaT Center for Human Genetics Tuebingen	RCV000172287	SCV004011261	benign	not provided	2023-11-01	criteria provided, single submitter	clinical testing	TTN: BS1, BS2
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000040471	SCV004038600	likely benign	not specified	2023-08-19	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000040471	SCV001920792	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000172287	SCV001976244	likely benign	not provided		no assertion criteria provided	clinical testing