Submissions for variant NM_001267550.2(TTN):c.26762-10_26762-9insTTGTTTTGTA

dbSNP: rs1553893826

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000460742	SCV000543167	likely benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-29	criteria provided, single submitter	clinical testing
GeneDx	RCV000480310	SCV000568172	likely benign	not specified	2017-12-28	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.
Genetic Services Laboratory, University of Chicago	RCV000480310	SCV000597667	likely benign	not specified	2016-12-23	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000727154	SCV000706197	uncertain significance	not provided	2017-02-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000480310	SCV004039494	benign	not specified	2023-08-14	criteria provided, single submitter	clinical testing	Variant summary: TTN c.23030-10_23030-9insTTTGTATTGT results in the insertion of 10 nucleotides at a position not widely known to affect splicing. Several computational tools predict a significant impact on normal splicing: four predict the variant weakens a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00037 in 149680 control chromosomes (i.e., 55 heterozygotes), predominantly at a frequency of 0.00053 within the Non-Finnish European subpopulation in the gnomAD database (v3.1.2). The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 1.4 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 Non-Finnish European origin. To our knowledge, no occurrence of c.23030-10_23030-9insTTTGTATTGT in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Four submitters have reported clinical-significance assessments for this variant to ClinVar after 2014; three submitters classified the variant as likely benign, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as benign.