Submissions for variant NM_001267550.2(TTN):c.30512-19dup

dbSNP: rs397517532

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000040108	SCV000063799	likely benign	not specified	2011-09-27	criteria provided, single submitter	clinical testing
GeneDx	RCV000423669	SCV000236630	benign	not provided	2018-06-11	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000396427	SCV000423781	likely benign	Dilated Cardiomyopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000307434	SCV000423782	likely benign	Early-onset myopathy with fatal cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000341302	SCV000423783	likely benign	Myopathy, myofibrillar, 9, with early respiratory failure	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000396421	SCV000423784	likely benign	Tibial muscular dystrophy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000359205	SCV000423786	likely benign	Limb-Girdle Muscular Dystrophy, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000423669	SCV000510581	benign	not provided	2017-02-16	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000040108	SCV001362650	benign	not specified	2019-08-19	criteria provided, single submitter	clinical testing	Variant summary: TTN c.26780-10dupT alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.1 in 201596 control chromosomes in the gnomAD database, including 809 homozygotes. The observed variant frequency is approximately 166 fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Cardiomyopathy phenotype (0.00063), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.26780-10dupT in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (2x) /likely benign (1x). Based on the evidence outlined above, the variant was classified as benign.
Invitae	RCV001517440	SCV001725929	benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001839575	SCV002101859	benign	Autosomal recessive limb-girdle muscular dystrophy type 2J	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000341302	SCV002101860	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000307434	SCV002101861	benign	Early-onset myopathy with fatal cardiomyopathy	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000396421	SCV002101862	benign	Tibial muscular dystrophy	2021-09-10	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000423669	SCV001742398	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000423669	SCV001798571	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000040108	SCV001923640	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000040108	SCV001967136	benign	not specified		no assertion criteria provided	clinical testing