Submissions for variant NM_001267550.2(TTN):c.11255-17_11255-16del

dbSNP: rs72647895

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000184122	SCV000236712	benign	not specified	2012-11-28	criteria provided, single submitter	clinical testing	The variant is found in DCM panel(s).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000184122	SCV001431994	benign	not specified	2020-08-10	criteria provided, single submitter	clinical testing	Variant summary: TTN c.10304-17_10304-16delAT alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 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 0.0006 in 243526 control chromosomes, predominantly at a frequency of 0.0088 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 22 fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Dilated Cardiomyopathy phenotype (0.00039), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.10304-17_10304-16delAT in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.
Genome-Nilou Lab	RCV001840291	SCV002100889	benign	Autosomal recessive limb-girdle muscular dystrophy type 2J	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001840292	SCV002100890	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001840293	SCV002100891	benign	Early-onset myopathy with fatal cardiomyopathy	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001840290	SCV002100892	benign	Tibial muscular dystrophy	2021-09-10	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002478631	SCV002803495	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	2021-11-26	criteria provided, single submitter	clinical testing
Invitae	RCV002516943	SCV003449317	benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV003736626	SCV004564525	benign	not provided	2023-10-10	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000184122	SCV001924189	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000184122	SCV001964929	benign	not specified		no assertion criteria provided	clinical testing