ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.32071G>A (p.Ala10691Thr)

gnomAD frequency: 0.00030  dbSNP: rs371452173
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Total submissions: 6
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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 RCV000154963 SCV000204645 likely benign not specified 2014-07-14 criteria provided, single submitter clinical testing Ala9447Thr in exon 122 of TTN: This variant is not expected to have clinical sig nificance due to a lack of conservation across species, including mammals. Of no te, multiple mammals (marmoset, pig, black fly fox, megabat, and elephant) have a threonine (Thr) at this position despite high nearby amino acid conservation. It has also been identified in 3/3716 African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs371452173).
Eurofins Ntd Llc (ga) RCV000724173 SCV000225730 uncertain significance not provided 2018-02-26 criteria provided, single submitter clinical testing
Invitae RCV001087214 SCV000555502 likely benign Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2024-01-08 criteria provided, single submitter clinical testing
GeneDx RCV000724173 SCV000979051 likely benign not provided 2018-04-23 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000154963 SCV002074530 likely benign not specified 2022-01-04 criteria provided, single submitter clinical testing Variant summary: TTN c.28339G>A (p.Ala9447Thr) results in a non-conservative amino acid change in the encoded protein sequence. Two of three in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00012 in 248638 control chromosomes, predominantly at a frequency of 0.00073 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Dilated Cardiomyopathy phenotype (0.00039), suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.28339G>A in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (likely benign n=2, VUS n=1). Based on the evidence outlined above, the variant was classified as likely benign.
Revvity Omics, Revvity RCV000724173 SCV003822352 uncertain significance not provided 2022-03-23 criteria provided, single submitter clinical testing

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