ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.91715dup (p.Asn30572fs) (rs779129892)

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Total submissions: 3
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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 RCV000209618 SCV000189760 uncertain significance 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.
Broad Institute Rare Disease Group,Broad Institute RCV000663410 SCV000786698 uncertain significance Limb-girdle muscular dystrophy, type 2J criteria provided, single submitter research The heterozygous p.Asn30572fs variant in TTN has been identified in the compound heterozygous state by our project in one individual with Limb Girdle Muscular Dystrophy. This variant has not been reported in the literature but compound heterozygous loss of function variants have been previously described in individuals with Limb Girdle Muscular Dystrophy (source: ClinVar). This variant has been entered in ClinVar in one unaffected person in DCM study (Variation ID 223353) and has been identified in 0.01% (1/15280) of African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs779129892). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain.
Blueprint Genetics RCV000788446 SCV000927561 likely pathogenic not provided 2018-03-02 criteria provided, single submitter clinical testing

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