Submissions for variant NM_001267550.2(TTN):c.69676A>G (p.Ser23226Gly)

gnomAD frequency: 0.00553  dbSNP: rs72646885

Total submissions: 27

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000040545	SCV000051713	benign	not specified	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000040545	SCV000064236	benign	not specified	2015-01-26	criteria provided, single submitter	clinical testing	p.Ser20658Gly in exon 274 of TTN: This variant is not expected to have clinical significance because it has been identified in 1.1% (182/16506) of South Asian c hromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute .org; dbSNP rs72646885).
GeneDx	RCV000040545	SCV000237474	benign	not specified	2016-06-28	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	RCV000231710	SCV000286803	benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000243089	SCV000318345	benign	Cardiovascular phenotype	2013-10-24	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.
Eurofins Ntd Llc (ga)	RCV000040545	SCV000332479	benign	not specified	2015-07-02	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769959	SCV000901385	benign	Cardiomyopathy	2016-11-17	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852817	SCV000995546	benign	Hypertrophic cardiomyopathy; Ventricular tachycardia; Familial dilated cardiomyopathy and peripheral neuropathy	2019-06-03	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001130328	SCV001289902	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	RCV001130329	SCV001289903	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	RCV001130330	SCV001289904	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.
Illumina Laboratory Services, Illumina	RCV001130331	SCV001289905	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	RCV001135375	SCV001295152	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000040545	SCV001361746	likely benign	not specified	2020-11-17	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001529677	SCV001474562	benign	not provided	2023-06-28	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001130329	SCV002100310	benign	Autosomal recessive limb-girdle muscular dystrophy type 2J	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001130330	SCV002100311	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001135375	SCV002100312	benign	Early-onset myopathy with fatal cardiomyopathy	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001130331	SCV002100314	benign	Tibial muscular dystrophy	2021-09-10	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001529677	SCV002496580	benign	not provided	2024-04-01	criteria provided, single submitter	clinical testing	TTN: PP3, BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV004541171	SCV004796140	benign	TTN-related disorder	2019-05-02	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).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529677	SCV001743532	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001529677	SCV001797687	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000040545	SCV001920371	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000040545	SCV001929534	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000040545	SCV001952771	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000040545	SCV001965574	benign	not specified		no assertion criteria provided	clinical testing