Submissions for variant NM_001267550.2(TTN):c.15542G>C (p.Gly5181Ala)

gnomAD frequency: 0.00108  dbSNP: rs201185434

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039872	SCV000063563	likely benign	not specified	2012-01-24	criteria provided, single submitter	clinical testing	p.Gly3937Ala in exon 50 of TTN: This variant is not expected to have clinical si gnificance because it is not located within the splice consensus sequence and ha s been identified in 0.4% (12/3164) of African American chromosomes by the NHLBI Exome Sequencing Project in a broad population (http://evs.gs.washington.edu/EV S).
Eurofins Ntd Llc (ga)	RCV000039872	SCV000114328	likely benign	not specified	2015-08-21	criteria provided, single submitter	clinical testing
GeneDx	RCV001703893	SCV000238219	likely benign	not provided	2020-03-16	criteria provided, single submitter	clinical testing
Invitae	RCV000459290	SCV000555535	likely benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-25	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000039872	SCV000616001	benign	not specified	2016-10-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001703893	SCV002048179	likely benign	not provided	2021-07-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001839488	SCV002100721	benign	Autosomal recessive limb-girdle muscular dystrophy type 2J	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001839489	SCV002100722	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001839490	SCV002100723	benign	Early-onset myopathy with fatal cardiomyopathy	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001839487	SCV002100724	benign	Tibial muscular dystrophy	2021-09-10	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000039872	SCV002571886	benign	not specified	2022-08-08	criteria provided, single submitter	clinical testing	Variant summary: TTN c.11810G>C (p.Gly3937Ala) results in a non-conservative amino acid change in the encoded protein sequence. The variant allele was found at a frequency of 0.00041 in 278438 control chromosomes, predominantly at a frequency of 0.0044 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 11-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 African or African-American origin. To our knowledge, no occurrence of c.11810G>C in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Six 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.
PreventionGenetics, part of Exact Sciences	RCV004534851	SCV004727671	likely benign	TTN-related disorder	2021-01-27	criteria provided, single submitter	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).
Clinical Genetics, Academic Medical Center	RCV000039872	SCV001978976	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001703893	SCV001979914	likely benign	not provided		no assertion criteria provided	clinical testing