Submissions for variant NM_001267550.2(TTN):c.53881+5G>A

gnomAD frequency: 0.00016  dbSNP: rs753527304

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000209576	SCV000189653	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.
Eurofins Ntd Llc (ga)	RCV000597330	SCV000702569	uncertain significance	not provided	2016-10-11	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000597330	SCV001501350	uncertain significance	not provided	2021-09-01	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000597330	SCV001714654	uncertain significance	not provided	2023-01-04	criteria provided, single submitter	clinical testing	BS1, BP4
GeneDx	RCV000597330	SCV001823705	uncertain significance	not provided	2019-12-24	criteria provided, single submitter	clinical testing	In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Reported previously in association with dilated cardiomyopathy, however, variant was also observed in healthy individuals in large population cohorts (Roberts et al., 2015; Akinrinade et al., 2016); Previously identified in the heterozygous state in one individual from a cohort of 172 women diagnosed with peripartum cardiomoypathy (Ware et al., 2016); This variant is associated with the following publications: (PMID: 25589632, 26777568, 26735901)
Ambry Genetics	RCV002426983	SCV002744157	likely benign	Cardiovascular phenotype	2020-07-22	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.
Fulgent Genetics, Fulgent Genetics	RCV002478753	SCV002778938	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9	2021-12-07	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000597330	SCV004237042	uncertain significance	not provided	2023-05-15	criteria provided, single submitter	clinical testing