Submissions for variant NM_001267550.2(TTN):c.2764C>T (p.Arg922Cys)

gnomAD frequency: 0.00123  dbSNP: rs72647862

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000222512	SCV000237554	likely benign	not specified	2017-10-23	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000222512	SCV000271004	likely benign	not specified	2015-01-05	criteria provided, single submitter	clinical testing	p.Arg922Cys in exon 16 of TTN: This variant is not expected to have clinical sig nificance because it has been identified in 0.5% (48/10580) of African chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs72647862).
Ambry Genetics	RCV000241772	SCV000320403	likely benign	Cardiovascular phenotype	2018-08-08	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Invitae	RCV000475691	SCV000555185	likely benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-24	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000222512	SCV000855075	likely benign	not specified	2017-11-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000222512	SCV001554510	likely benign	not specified	2024-04-01	criteria provided, single submitter	clinical testing	Variant summary: TTN c.2764C>T (p.Arg922Cys) results in a non-conservative amino acid change located in the near Z-disk region of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00033 in 250426 control chromosomes, predominantly at a frequency of 0.0046 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. To our knowledge, no occurrences of c.2764C>T in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating an impact on protein function have been reported in the literature. ClinVar contains an entry for this variant (Variation ID: 202868). Based on the evidence outlined above, the variant was classified as likely benign.
CeGaT Center for Human Genetics Tuebingen	RCV001726031	SCV004700170	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	TTN: BP4
PreventionGenetics, part of Exact Sciences	RCV004539723	SCV004780148	likely benign	TTN-related disorder	2021-06-15	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	RCV000222512	SCV001924849	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001726031	SCV001965875	likely benign	not provided		no assertion criteria provided	clinical testing