Submissions for variant NM_001267550.2(TTN):c.70696G>C (p.Gly23566Arg)

gnomAD frequency: 0.01212  dbSNP: rs55801134

Total submissions: 27

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000040560	SCV000051756	benign	not specified	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000040560	SCV000064251	benign	not specified	2012-06-11	criteria provided, single submitter	clinical testing	Gly20998Arg in Exon 275 of TTN: This variant is not expected to have clinical si gnificance because it has been identified in 1.5% (102/6822) of European America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs55801134).
GeneDx	RCV000040560	SCV000169349	benign	not specified	2014-01-03	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.
Invitae	RCV000229769	SCV000286811	benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-31	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003891500	SCV000315544	benign	TTN-related condition	2019-06-13	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Ambry Genetics	RCV000249212	SCV000317479	benign	Cardiovascular phenotype	2013-01-16	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.
Illumina Laboratory Services, Illumina	RCV000342774	SCV000422011	likely benign	Early-onset myopathy with fatal cardiomyopathy	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000405582	SCV000422012	likely benign	Dilated cardiomyopathy 1G	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000303193	SCV000422013	benign	Tibial muscular dystrophy	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000346389	SCV000422014	likely benign	Autosomal recessive limb-girdle muscular dystrophy type 2J	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000310303	SCV000422016	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Eurofins Ntd Llc (ga)	RCV000040560	SCV000707438	benign	not specified	2017-04-04	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000993477	SCV001146476	benign	not provided	2019-07-24	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000993477	SCV001156931	benign	not provided	2023-11-15	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000040560	SCV001431947	likely benign	not specified	2020-08-16	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000346389	SCV002100283	benign	Autosomal recessive limb-girdle muscular dystrophy type 2J	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000310303	SCV002100284	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000342774	SCV002100285	benign	Early-onset myopathy with fatal cardiomyopathy	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000303193	SCV002100286	benign	Tibial muscular dystrophy	2021-09-10	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000993477	SCV002544145	benign	not provided	2024-03-01	criteria provided, single submitter	clinical testing	TTN: BS1, BS2
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003486595	SCV004240090	benign	Cardiomyopathy	2022-11-30	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000040560	SCV000153335	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000993477	SCV001744109	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000993477	SCV001798677	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000040560	SCV001929308	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000040560	SCV001969525	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000040560	SCV001979152	benign	not specified		no assertion criteria provided	clinical testing