Submissions for variant NM_001267550.2(TTN):c.79612A>G (p.Thr26538Ala)

gnomAD frequency: 0.00100  dbSNP: rs150682764

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000172632	SCV000054929	likely benign	not provided	2013-06-24	criteria provided, single submitter	research
Eurofins Ntd Llc (ga)	RCV000176834	SCV000228579	likely benign	not specified	2015-02-06	criteria provided, single submitter	clinical testing
GeneDx	RCV000172632	SCV000237589	likely benign	not provided	2021-03-05	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 23861362)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000176834	SCV000271083	likely benign	not specified	2015-04-13	criteria provided, single submitter	clinical testing	p.Thr23970Ala in exon 275 of TTN: This variant is not expected to have clinical significance because it has been identified in 0.5% (47/9800) of African chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs150682764).
Invitae	RCV001086126	SCV000286846	benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-30	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769938	SCV000901364	likely benign	Cardiomyopathy	2017-08-18	criteria provided, single submitter	clinical testing
Genetics and Genomics Program, Sidra Medicine	RCV001293185	SCV001434183	likely benign	Primary dilated cardiomyopathy		criteria provided, single submitter	research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000176834	SCV001478613	benign	not specified	2021-03-18	criteria provided, single submitter	clinical testing	Variant summary: TTN c.71908A>G (p.Thr23970Ala) results in a non-conservative amino acid change located in the A-band region of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00032 in 248318 control chromosomes, predominantly at a frequency of 0.0047 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 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. To our knowledge, no occurrence of c.71908A>G in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Five ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Athena Diagnostics	RCV000176834	SCV001879702	benign	not specified	2021-05-13	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001840211	SCV002100128	benign	Autosomal recessive limb-girdle muscular dystrophy type 2J	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001840212	SCV002100129	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001840213	SCV002100130	benign	Early-onset myopathy with fatal cardiomyopathy	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001840210	SCV002100131	benign	Tibial muscular dystrophy	2021-09-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002336415	SCV002645374	benign	Cardiovascular phenotype	2018-02-28	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV004539590	SCV004788995	likely benign	TTN-related disorder	2019-03-25	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	RCV000176834	SCV001918229	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000176834	SCV001932229	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000172632	SCV001969959	likely benign	not provided		no assertion criteria provided	clinical testing