Submissions for variant NM_001267550.2(TTN):c.34769A>G (p.Glu11590Gly)

gnomAD frequency: 0.00192  dbSNP: rs201167067

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000040176	SCV000063867	likely benign	not specified	2012-04-11	criteria provided, single submitter	clinical testing	Glu10289Gly in exon 147 of TTN: This variant is not expected to have clinical si gnificance because it has been identified in 0.4% (13/2934) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS/) Glu10289Gly in exon 147 of TTN (allele frequenc y = 0.4%, 13/2934) **
Eurofins Ntd Llc (ga)	RCV000040176	SCV000203721	benign	not specified	2016-08-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000040176	SCV000237112	benign	not specified	2015-10-29	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.
Invitae	RCV001081714	SCV000555390	benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-31	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000468589	SCV001146379	benign	not provided	2018-12-27	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000468589	SCV001477827	likely benign	not provided	2023-11-22	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001839589	SCV002101396	benign	Autosomal recessive limb-girdle muscular dystrophy type 2J	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001839590	SCV002101397	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001839591	SCV002101398	benign	Early-onset myopathy with fatal cardiomyopathy	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001839588	SCV002101399	benign	Tibial muscular dystrophy	2021-09-10	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000040176	SCV002547662	benign	not specified	2022-05-09	criteria provided, single submitter	clinical testing	Variant summary: TTN c.30866A>G (p.Glu10289Gly) results in a non-conservative amino acid change located in the I-band region of the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00039 in 235532 control chromosomes, predominantly at a frequency of 0.0058 within the African or African-American subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 15 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.30866A>G 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.
Fulgent Genetics, Fulgent Genetics	RCV002490557	SCV002803006	likely benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9	2021-09-16	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003486583	SCV004239894	benign	Cardiomyopathy	2022-12-12	criteria provided, single submitter	clinical testing