ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.85090C>T (p.Arg28364Ter) (rs770038577)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000209383 SCV000189667 likely pathogenic Primary dilated cardiomyopathy 2014-10-08 criteria provided, single submitter research This TTN truncating variant (TTNtv) was identified in one individual in this cohort and is located in an exon that is highly expressed in the heart. In the seven cohorts assessed, TTNtv were found in 14% of ambulant DCM, 22% end-stage or familial DCM, and 2% controls. Heterozygous nonsense, frameshift and canonical splice-disrupting variants found in constitutive and other highly utilised exons are highly likely to be pathogenic when identified in individuals with phenotypically confirmed DCM. TTNtv found incidentally in healthy individuals (excluding familial assessment of DCM relatives) are thought to have low penetrance, particularly when identified in exons that are not constitutively expressed in the heart.
Ambry Genetics RCV000243897 SCV000320220 likely pathogenic Cardiovascular phenotype 2016-08-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000476159 SCV000542814 pathogenic Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2018-12-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 28364 (p.Arg28364*) of the TTN gene. It is expected to result in an absent or disrupted protein product. This variant is found in the A-band of this gene. Truncating variants in the A-band of TTN are significantly overrepresented in patients with dilated cardiomyopathy and are considered to be pathogenic for the disease (PMID: 25589632). This particular variant has been reported in the literature in an individual with dilated cardiomyopathy (PMID: 25589632). ClinVar contains an entry for this variant (Variation ID: 223295). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV000788393 SCV000927482 likely pathogenic not provided 2017-11-24 criteria provided, single submitter clinical testing

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