Submissions for variant NM_001267550.2(TTN):c.17300G>A (p.Ser5767Asn)

gnomAD frequency: 0.00107  dbSNP: rs200692495

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039896	SCV000063587	likely benign	not specified	2012-01-24	criteria provided, single submitter	clinical testing	p.Ser4523Asn in exon 56 of TTN: This variant is not expected to have clinical si gnificance because it has been identified in 0.4% (13/3160) of African American chromosomes by the NHLBI Exome Sequencing Project in a broad population (http:// evs.gs.washington.edu/EVS).
Eurofins Ntd Llc (ga)	RCV000039896	SCV000114332	likely benign	not specified	2015-08-21	criteria provided, single submitter	clinical testing
GeneDx	RCV001703894	SCV000238239	likely benign	not provided	2020-03-16	criteria provided, single submitter	clinical testing
Invitae	RCV000462843	SCV000555023	likely benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-24	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000039896	SCV000616008	benign	not specified	2016-10-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001703894	SCV002049540	likely benign	not provided	2021-07-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001839512	SCV002100025	benign	Autosomal recessive limb-girdle muscular dystrophy type 2J	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001839513	SCV002100026	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001839514	SCV002100027	benign	Early-onset myopathy with fatal cardiomyopathy	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001839511	SCV002100028	benign	Tibial muscular dystrophy	2021-09-10	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000039896	SCV002571885	likely benign	not specified	2022-08-08	criteria provided, single submitter	clinical testing	Variant summary: TTN c.13568G>A (p.Ser4523Asn) results in a conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00031 in 248614 control chromosomes, predominantly at a frequency of 0.0047 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 12-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. c.13568G>A has been reported in the literature in individual(s) affected with Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia (Fedida_2017). These report(s) do not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV004534858	SCV004731127	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	RCV000039896	SCV001979147	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001703894	SCV001979838	likely benign	not provided		no assertion criteria provided	clinical testing