Submissions for variant NM_001267550.2(TTN):c.26762-39TTTGT[8]

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	RCV000154085	SCV000269935	benign	not specified	2015-06-25	criteria provided, single submitter	clinical testing	c.23030-39TTTGT[8] in intron 89 of TTN: This variant is part of a 5 bp repeat (T TTGT) and adds 2 repeat units to 6 present in the reference sequence. It is not expected to have clinical significance because it has been identified in 3.9% (8 2/2118) of African chromosomes (ExAC, http://exac.broadinstitute.org; dbSNP rs71 393436). Although this variant is located in the splice region, computational to ols do not predict an effect.
Invitae	RCV000229535	SCV000286542	benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-02-01	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000154085	SCV000334821	benign	not specified	2015-09-15	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000406361	SCV000423950	likely benign	Limb-Girdle Muscular Dystrophy, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000307593	SCV000423951	likely benign	Hypertrophic cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000366602	SCV000423952	likely benign	Dilated Cardiomyopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000264937	SCV000423953	likely benign	Myopathy, myofibrillar, 9, with early respiratory failure	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000303613	SCV000423954	likely benign	Tibial muscular dystrophy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000360730	SCV000423955	likely benign	Early-onset myopathy with fatal cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769909	SCV000901335	benign	Cardiomyopathy	2020-01-23	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000154085	SCV001363774	benign	not specified	2019-08-19	criteria provided, single submitter	clinical testing	Variant summary: TTN c.23030-19_23030-10dup10 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 0.0069 in 131482 control chromosomes, predominantly at a frequency of 0.043 within the African or African-American subpopulation in the gnomAD database, including 12 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 69-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 African or African-American origin. Five ClinVar submissions (evaluation after 2014) cites the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as benign.
GeneDx	RCV001711422	SCV001941519	benign	not provided	2020-08-26	criteria provided, single submitter	clinical testing