Submissions for variant NM_001267550.2(TTN):c.20630T>C (p.Ile6877Thr)

gnomAD frequency: 0.00103  dbSNP: rs142794598

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000172693	SCV000055056	likely benign	not provided	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154985	SCV000204667	likely benign	not specified	2015-04-24	criteria provided, single submitter	clinical testing	p.Ile5633Thr in exon 68 of TTN: This variant is not expected to have clinical si gnificance because it has been identified in 0.4% (37/9774) of African chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs142794598).
Eurofins Ntd Llc (ga)	RCV000154985	SCV000231970	likely benign	not specified	2017-01-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000172693	SCV000238284	likely benign	not provided	2021-06-24	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 23861362)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081624	SCV000555280	likely benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2025-02-03	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000172693	SCV000616019	likely benign	not provided	2018-03-23	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000172693	SCV001473651	likely benign	not provided	2024-05-15	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000154985	SCV002555937	likely benign	not specified	2025-04-04	criteria provided, single submitter	clinical testing	Variant summary: TTN c.16898T>C (p.Ile5633Thr) results in a non-conservative amino acid change located in the I-band of the encoded protein sequence. Two of three in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00027 in 247418 control chromosomes, predominantly at a frequency of 0.0038 within the African or African-American subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 10-fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Dilated Cardiomyopathy phenotype (0.00039). To our knowledge, no occurrence of c.16898T>C in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 178246). Based on the evidence outlined above, the variant was classified as likely benign.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003486695	SCV004239845	benign	Cardiomyopathy	2023-05-16	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004534980	SCV004740629	likely benign	TTN-related disorder	2022-03-18	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).