Submissions for variant NM_001267550.2(TTN):c.1398+16C>T

gnomAD frequency: 0.00124  dbSNP: rs144043280

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000125776	SCV000169243	benign	not specified	2014-04-29	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000125776	SCV001363936	benign	not specified	2019-10-08	criteria provided, single submitter	clinical testing	Variant summary: TTN c.1398+16C>T 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 0.0042 in 250880 control chromosomes, predominantly at a frequency of 0.023 within the South Asian subpopulation in the gnomAD database, including 14 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 37-folds over the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Cardiomyopathy phenotype (0.00063), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001528473	SCV001472760	benign	not provided	2020-03-12	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001839949	SCV002101629	benign	Autosomal recessive limb-girdle muscular dystrophy type 2J	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001839950	SCV002101630	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001839951	SCV002101631	benign	Early-onset myopathy with fatal cardiomyopathy	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001839948	SCV002101632	benign	Tibial muscular dystrophy	2021-09-10	criteria provided, single submitter	clinical testing
Invitae	RCV002055604	SCV002433187	benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-31	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528473	SCV001740273	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000125776	SCV001923028	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000125776	SCV001966292	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001528473	SCV002036480	likely benign	not provided		no assertion criteria provided	clinical testing