ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.34856-17A>G

gnomAD frequency: 0.00042  dbSNP: rs188686309
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000605739 SCV000730360 benign not specified 2017-04-11 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001811118 SCV001473289 likely benign not provided 2020-01-16 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001840710 SCV002101391 benign Autosomal recessive limb-girdle muscular dystrophy type 2J 2021-09-10 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001840711 SCV002101393 benign Myopathy, myofibrillar, 9, with early respiratory failure 2021-09-10 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001840712 SCV002101394 benign Early-onset myopathy with fatal cardiomyopathy 2021-09-10 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001840709 SCV002101395 benign Tibial muscular dystrophy 2021-09-10 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000605739 SCV002104061 benign not specified 2022-02-07 criteria provided, single submitter clinical testing Variant summary: TTN c.30953-17A>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00011 in 241732 control chromosomes, predominantly at a frequency of 0.0017 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 4 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.30953-17A>G in individuals affected with Dilated Cardiomyopathy/Limb Girdle Muscular Dystrophy/TTN-related disorders and no experimental evidence demonstrating its impact on protein function have been reported. Two 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.
Invitae RCV002066770 SCV002367074 likely benign Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2021-12-15 criteria provided, single submitter clinical testing

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