ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.52021C>T (p.Arg17341Ter)

gnomAD frequency: 0.00001  dbSNP: rs926741242
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000459936 SCV000543001 pathogenic Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2024-09-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg17341*) in the TTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. This variant is present in population databases (no rsID available, gnomAD 0.001%). This premature translational stop signal has been observed in individual(s) with atrial fibrillation and/or autosomal recessive early-adult onset distal myopathy (PMID: 30365001, 30535219). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 405082). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant is located in the A band of TTN (PMID: 25589632). Truncating variants in this region are significantly overrepresented in patients affected with dilated cardiomyopathy (PMID: 25589632). Truncating variants in this region have also been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875). For these reasons, this variant has been classified as Pathogenic.
Center for Human Genetics, University of Leuven RCV003237347 SCV002817390 likely pathogenic Primary dilated cardiomyopathy 2022-12-31 criteria provided, single submitter clinical testing
Muscle and Diseases Team, Institut de Génétique et Biologie Moléculaire et Cellulaire RCV004586715 SCV005038520 likely pathogenic Centronuclear myopathy 2024-03-01 criteria provided, single submitter research PVS1+PM2

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