Submissions for variant NM_001267550.2(TTN):c.69904G>A (p.Val23302Ile)

gnomAD frequency: 0.00036  dbSNP: rs190421400

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000040549	SCV000064240	uncertain significance	not specified	2016-04-29	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Val20734Ile v ariant in TTN has been reported in 1 individual with HCM (LMM data). This varian t has also been identified in 0.2% (16/9674) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs190421400 ). Valine (Val) at position 20734 is not conserved in mammals (chimp carries an isoleucine (Ile)), which raises the possibility that this change may be tolerate d. Computational prediction tools suggest that the p.Val20734Ile variant may not impact the protein, though this information is not predictive enough to rule ou t pathogenicity. In summary, while the clinical significance of the p.Val20734Il e variant is uncertain, its frequency suggests that it is more likely to be beni gn.
Ambry Genetics	RCV000246349	SCV000318815	likely benign	Cardiovascular phenotype	2019-04-03	criteria provided, single submitter	clinical testing	In silico models in agreement (benign);Subpopulation frequency in support of benign classification
Labcorp Genetics (formerly Invitae), Labcorp	RCV001088941	SCV000643593	likely benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-31	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000726999	SCV000704825	uncertain significance	not provided	2017-01-04	criteria provided, single submitter	clinical testing
GeneDx	RCV000726999	SCV000730933	likely benign	not provided	2020-10-14	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149656	SCV003837977	benign	Cardiomyopathy	2021-11-25	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000726999	SCV001920291	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000040549	SCV001929248	benign	not specified		no assertion criteria provided	clinical testing