Submissions for variant NM_001267550.2(TTN):c.26762-39TTTGT[7]

dbSNP: rs71393436

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000040059	SCV000063750	benign	not specified	2017-08-10	criteria provided, single submitter	clinical testing	c.23030-39TTTGT[7] in intron 89 of TTN: This variant is part of a 5-bp repeat ( TTTGT) and adds one repeat unit to the 6 present in the reference sequence. Alt hough this variant is located in the splice region, computational tools do not p redict an effect. This variant is not expected to have clinical significance bec ause similar variants within this repeat region have been identified in 0.4% ( 6 5/15162) of African chromosomes by the Genome Aggregation Database (gnomAD, http ://gnomad.broadinstitute.org; dbSNP rs79799565). Additionally, this variant has been identified in 231 individuals by our laboratory, at least 37 of which were found to have an alternate cause for disease.
GeneDx	RCV000040059	SCV000236747	benign	not specified	2014-08-21	criteria provided, single submitter	clinical testing	The variant is found in CARDIOMYOPATHY panel(s).
Genetic Services Laboratory, University of Chicago	RCV000040059	SCV000249246	likely benign	not specified	2015-03-23	criteria provided, single submitter	clinical testing
Invitae	RCV000205385	SCV000262475	benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2023-09-11	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000373966	SCV000423944	likely benign	Tibial muscular dystrophy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000281725	SCV000423945	likely benign	Limb-Girdle Muscular Dystrophy, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000348484	SCV000423946	likely benign	Early-onset myopathy with fatal cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000313240	SCV000423948	likely benign	Myopathy, myofibrillar, 9, with early respiratory failure	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000351759	SCV000423949	likely benign	Dilated Cardiomyopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769908	SCV000901334	benign	Cardiomyopathy	2016-10-07	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000040059	SCV001362649	benign	not specified	2019-08-19	criteria provided, single submitter	clinical testing	Variant summary: TTN c.23030-14_23030-10dupTTTGT 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 0.2 in 131482 control chromosomes in the gnomAD database, including 3533 homozygotes. The observed variant frequency is approximately 315 fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Cardiomyopathy phenotype (0.00063), strongly suggesting that the variant is benign. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Eurofins Ntd Llc (ga)	RCV000040059	SCV000203730	benign	not specified	2014-01-13	no assertion criteria provided	clinical testing