Submissions for variant NM_001267550.2(TTN):c.51931G>T (p.Glu17311Ter)

dbSNP: rs2154198430

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001797950	SCV002041818	likely pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2J	2021-11-05	criteria provided, single submitter	clinical testing	Variant summary: TTN c.44227G>T (p.Glu14743X) in exon 222 results in a premature termination codon in the A-band region of the titin protein and is predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This exon is a constitutively expressed exon as evidenced by a high PSI (percentage spliced in) score for exon usage in the human left ventricle, derived from patients with Dialted Cardiomyopathy (DCM). The variant was absent in 247994 control chromosomes. To our knowledge, no occurrence of c.44227G>T in individuals affected with Limb-Girdle Muscular Dystrophy, Type 2J/Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.