Submissions for variant NM_001267550.2(TTN):c.34660GAA[1] (p.Glu11555del)

dbSNP: rs763098227

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000274162	SCV000336573	uncertain significance	not provided	2015-10-16	criteria provided, single submitter	clinical testing
Invitae	RCV000474545	SCV000542785	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-11-01	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769041	SCV000900414	uncertain significance	Cardiomyopathy	2021-10-06	criteria provided, single submitter	clinical testing
GeneDx	RCV000274162	SCV000977097	uncertain significance	not provided	2019-09-16	criteria provided, single submitter	clinical testing	In-frame deletion of one amino acid in a non-repeat region; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Not located in the A-band nor the M-line region of titin, where the majority of pathogenic truncating variants have been reported; Identified in a patient with hypertrophic cardiomyopathy in published literature (Sanchez et al., 2016); This variant is associated with the following publications: (PMID: 27930701)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001582909	SCV001821438	likely benign	not specified	2021-08-30	criteria provided, single submitter	clinical testing	Variant summary: TTN c.30760_30762delGAA (p.Glu10254del) results in an in-frame deletion that is predicted to remove one amino acid from I-band domain of the encoded protein. The variant allele was found at a frequency of 0.00026 in 151610 control chromosomes, predominantly at a frequency of 0.0005 within the Non-Finnish European subpopulation in the gnomAD database (gnomAD v3). The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 1.3 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. c.30760_30762delGAA has been reported in the literature in one individual affected with Hypertrophy Cardiomyopathy and one individual who was tested for Cardiomyopathy panel and without specified phenotype (Sanchez_2016, Fedida_2017). These reports do not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=3) and likely benign (n=1). Based on the evidence outlined above, the variant was classified as likely benign.
Revvity Omics, Revvity	RCV000274162	SCV003824852	uncertain significance	not provided	2023-02-24	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000274162	SCV004152474	likely benign	not provided	2023-10-01	criteria provided, single submitter	clinical testing	TTN: BP4