ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.58612A>G (p.Thr19538Ala)

gnomAD frequency: 0.00154  dbSNP: rs200017524
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000154937 SCV000204619 likely benign not specified 2015-10-31 criteria provided, single submitter clinical testing p.Thr16970Ala in exon 247 of TTN: This variant is not expected to have clinical significance because it has been identified in 0.5% (45/9792) of African chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs200017524).
GeneDx RCV000154937 SCV000237346 likely benign not specified 2018-01-11 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.
Eurofins Ntd Llc (ga) RCV000154937 SCV000335002 likely benign not specified 2015-09-08 criteria provided, single submitter clinical testing
Invitae RCV001082823 SCV000555270 benign Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2024-01-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV000622130 SCV000736507 likely benign Cardiovascular phenotype 2018-07-09 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.
Athena Diagnostics RCV000714058 SCV000844724 benign not provided 2018-07-20 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001840144 SCV002100420 benign Autosomal recessive limb-girdle muscular dystrophy type 2J 2021-09-10 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001840145 SCV002100422 benign Myopathy, myofibrillar, 9, with early respiratory failure 2021-09-10 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001840146 SCV002100423 benign Early-onset myopathy with fatal cardiomyopathy 2021-09-10 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001840143 SCV002100424 benign Tibial muscular dystrophy 2021-09-10 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000154937 SCV004021274 benign not specified 2023-06-12 criteria provided, single submitter clinical testing Variant summary: TTN c.50908A>G (p.Thr16970Ala) results in a non-conservative amino acid change located in the A-band region of the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00036 in 248186 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. To our knowledge, no occurrence of c.50908A>G in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and all laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
PreventionGenetics, part of Exact Sciences RCV004544424 SCV004769340 likely benign TTN-related disorder 2020-11-10 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).

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