Submissions for variant NM_001267550.2(TTN):c.18390A>T (p.Thr6130=)

gnomAD frequency: 0.01518  dbSNP: rs66523653

Total submissions: 22

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039908	SCV000063599	benign	not specified	2012-04-24	criteria provided, single submitter	clinical testing	Thr4886Thr in Exon 60 of TTN: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 4.2% (128/3084) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS/; rs66523653).
GeneDx	RCV000039908	SCV000169599	benign	not specified	2014-01-15	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.
PreventionGenetics, part of Exact Sciences	RCV004528202	SCV000315410	benign	TTN-related disorder	2019-05-20	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).
Illumina Laboratory Services, Illumina	RCV000310471	SCV000424532	benign	Tibial muscular dystrophy	2018-01-13	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	RCV000362872	SCV000424533	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2018-01-13	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	RCV000304188	SCV000424535	benign	Early-onset myopathy with fatal cardiomyopathy	2018-01-13	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	RCV000361210	SCV000424536	benign	Autosomal recessive limb-girdle muscular dystrophy type 2J	2018-01-13	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	RCV000264193	SCV000424537	likely benign	Dilated cardiomyopathy 1G	2018-01-13	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.
Invitae	RCV000474141	SCV000555070	benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000039908	SCV001362718	benign	not specified	2019-09-14	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000361210	SCV002099985	benign	Autosomal recessive limb-girdle muscular dystrophy type 2J	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000362872	SCV002099986	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000304188	SCV002099987	benign	Early-onset myopathy with fatal cardiomyopathy	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000310471	SCV002099988	benign	Tibial muscular dystrophy	2021-09-10	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001530120	SCV003799655	benign	not provided	2023-09-22	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000039908	SCV000153181	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	RCV001530120	SCV001744777	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000039908	SCV001921549	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000039908	SCV001953331	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000039908	SCV001967780	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001530120	SCV001978441	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001530120	SCV002036093	likely benign	not provided		no assertion criteria provided	clinical testing