Submissions for variant NM_133379.5(TTN):c.15285_15317dup (p.5058TLERYSTPPGE[6])

dbSNP: rs397517815

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041053	SCV000064744	likely benign	not specified	2015-04-09	criteria provided, single submitter	clinical testing	p.Thr5102_Glu5112dup in exon 45A of TTN: This variant is not expected to be clin ically significant because it has been identified in 0.6% (376/66452) European c hromosomes, including 2 homozygotes, by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs397517815) and in 1.1% (4/372) Caucasian control chromosomes tested by our laboratory (LMM unpublished data).
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000041053	SCV000740483	likely benign	not specified	2017-01-17	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000786262	SCV001334681	likely benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	TTN: PM4, BS2
GeneDx	RCV000786262	SCV001847297	benign	not provided	2019-10-23	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002496655	SCV002804680	likely benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9	2022-02-15	criteria provided, single submitter	clinical testing
Stanford Center for Inherited Cardiovascular Disease, Stanford University	RCV000786262	SCV000925013	uncertain significance	not provided	2016-07-27	no assertion criteria provided	provider interpretation	p.Thr5102_Glu5112dup (T5102_E5112dup, c.15285_15317dup33:) in exon 46 of the TTN gene (NM_133379.3, alternate transcript). Seen in a patient in our center with LVNC and reduced systolic function. Given the location, lack of case data, and frequency in ExAC, we consider this variant a variant of uncertain significance, probably benign and we do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). The variant has not been reported in association with disease. Based on the genomic position (hg19 ) and https://cardiodb.org/titin/ it appears the variant is in the I-band distant from the A band. To date it appears that pathogenic variants in TTN are in the A band (or the I band near the A band). ExAC: 0.6% (376/66452) European chromosomes.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000786262	SCV001800155	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000041053	SCV001920706	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000786262	SCV001953317	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000041053	SCV001975692	benign	not specified		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004537134	SCV004741583	likely benign	TTN-related disorder	2019-08-30	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).