Submissions for variant NM_001267550.2(TTN):c.66692G>A (p.Arg22231His)

gnomAD frequency: 0.00119  dbSNP: rs200971254

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000040510	SCV000064201	likely benign	not specified	2015-08-12	criteria provided, single submitter	clinical testing	p.Arg19663His in exon 265 in TTN: This variant is not expected to have clinical significance because it has been identified in 0.4% (37/9764) of African chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs200971254).
GeneDx	RCV000040510	SCV000236674	benign	not specified	2014-10-07	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.
Eurofins Ntd Llc (ga)	RCV000040510	SCV000335311	likely benign	not specified	2015-09-10	criteria provided, single submitter	clinical testing
Invitae	RCV001082762	SCV000555578	likely benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000619559	SCV000736829	likely benign	Cardiovascular phenotype	2018-12-13	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Athena Diagnostics Inc	RCV000459532	SCV001146467	benign	not provided	2019-06-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001132756	SCV001292427	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-04-28	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	RCV001132757	SCV001292428	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2017-09-24	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	RCV001136161	SCV001295983	likely benign	Dilated cardiomyopathy 1G	2017-09-24	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	RCV001136162	SCV001295984	uncertain significance	Early-onset myopathy with fatal cardiomyopathy	2017-04-28	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	RCV001136163	SCV001295985	benign	Tibial muscular dystrophy	2017-09-24	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	RCV001170580	SCV001333168	benign	Cardiomyopathy	2018-03-29	criteria provided, single submitter	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000459532	SCV001797744	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000040510	SCV001920035	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000459532	SCV001931945	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000459532	SCV001968922	likely benign	not provided		no assertion criteria provided	clinical testing