Submissions for variant NM_001267550.2(TTN):c.26762-39TTTGT[12]

dbSNP: rs71393436

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000456665	SCV000554985	likely benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001194409	SCV001363942	benign	not specified	2019-11-06	criteria provided, single submitter	clinical testing	Variant summary: TTN c.23030-39_23030-10dup30 alters a 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 0.0012 in 100440 control chromosomes, predominantly at a frequency of 0.012 within the East Asian subpopulation in the gnomAD database, including 4 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 19-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 East Asian origin. To our knowledge, no occurrence of c.23030-39_23030-10dup30 in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission (evaluation after 2014) cites the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
GeneDx	RCV001551323	SCV001771805	likely benign	not provided	2019-11-05	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001551323	SCV002822757	benign	not provided	2022-11-01	criteria provided, single submitter	clinical testing	TTN: BS1, BS2
Clinical Genetics, Academic Medical Center	RCV001194409	SCV001924369	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001194409	SCV001974483	benign	not specified		no assertion criteria provided	clinical testing