Submissions for variant NM_001267550.2(TTN):c.24505+13C>T

gnomAD frequency: 0.00012  dbSNP: rs534803807

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000214424	SCV000270993	likely benign	not specified	2015-10-01	criteria provided, single submitter	clinical testing	c.20773+13C>T in intron 81 of TTN: This variant is not expected to have clinica l significance because a C>T change at this position does not diverge from the s plice consensus sequence and is therefore unlikely to impact splicing. It has be en identified in 0.2% (15/8606) of East Asian chromosomes by the Exome Aggregati on Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs534803807).
PreventionGenetics, part of Exact Sciences	RCV000214424	SCV000315427	likely benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000214424	SCV000730349	benign	not specified	2017-03-09	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000214424	SCV001821439	benign	not specified	2021-08-30	criteria provided, single submitter	clinical testing	Variant summary: TTN c.20773+13C>T 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. 4/4 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 0.00023 in 247558 control chromosomes, predominantly at a frequency of 0.0017 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 4.35 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 East Asian origin. To our knowledge, no occurrence of c.20773+13C>T in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two 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.
Genome-Nilou Lab	RCV001840345	SCV002099784	benign	Autosomal recessive limb-girdle muscular dystrophy type 2J	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001840346	SCV002099785	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001840347	SCV002099786	benign	Early-onset myopathy with fatal cardiomyopathy	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001840344	SCV002099787	benign	Tibial muscular dystrophy	2021-09-10	criteria provided, single submitter	clinical testing
Invitae	RCV002057154	SCV002472446	likely benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-12	criteria provided, single submitter	clinical testing