Submissions for variant NM_001267550.2(TTN):c.101019_101020dup (p.Arg33674fs)

dbSNP: rs886041287

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000280520	SCV000329635	pathogenic	not provided	2015-07-16	criteria provided, single submitter	clinical testing	The c.96096_96097dupCA variant in the TTN gene has not been reported previously as a disease-causing variant nor as a benign polymorphism, to our knowledge. The c.96096_96097dupCA variant causes a frameshift starting with codon Arginine 32033 changes this amino acid to a Threonine residue, and creates a premature Stop codon at position 36 of the new reading frame, denoted p.Arg32033ThrfsX36. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. It is located within the region of the A-band where protein truncating pathogenic variants have been reported to be associated with TTN-related disorders. The c.96096_96097dupCA variant was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.96096_96097dupCA as a pathogenic variant.
Center for Personalized Medicine, Children's Hospital Los Angeles	RCV000584764	SCV000692556	likely pathogenic	Congenital muscular dystrophy; Scoliosis; Broad-based gait; Delayed gross motor development; Distal muscle weakness; Gowers sign; Severe muscular hypotonia; Heart murmur	2016-02-19	criteria provided, single submitter	clinical testing