Submissions for variant NM_001267550.2(TTN):c.40223A>G (p.Glu13408Gly)

gnomAD frequency: 0.00132  dbSNP: rs183950862

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000204258	SCV000261796	likely benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001531940	SCV001747287	likely benign	not provided	2023-04-01	criteria provided, single submitter	clinical testing	TTN: BP4, BS1
GeneDx	RCV001531940	SCV001785099	likely benign	not provided	2020-06-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001795338	SCV003928671	uncertain significance	not specified	2023-04-20	criteria provided, single submitter	clinical testing	Variant summary: TTN c.32594-529A>G is located at a position not widely known to affect splicing. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0002 in 147834 control chromosomes, predominantly at a frequency of 0.0034 within the African or African-American subpopulation in the gnomAD database. c.32594-529A>G has been reported in the literature in an individuals affected with cerebral palsy and authors classified the variant as uncertain significance (example: Pingel_2018). This report does not provide unequivocal conclusions about association of the variant with Limb-Girdle Muscular Dystrophy, Type 2J. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely benign (n=2) and VUS (n=1). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Clinical Genetics, Academic Medical Center	RCV001795338	SCV002034561	benign	not specified		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001531940	SCV002035034	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001531940	SCV002038016	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004530241	SCV004766417	likely benign	TTN-related disorder	2020-02-18	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).