Submissions for variant NM_001267550.2(TTN):c.107890C>T (p.Gln35964Ter)

dbSNP: rs281864929

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003234934	SCV003934164	uncertain significance	not specified	2025-01-15	criteria provided, single submitter	clinical testing	Variant summary: TTN c.100186C>T (p.Gln33396X) results in a premature termination codon, predicted to cause a truncation of the encoded protein, however nonsense mediated decay is not predicted. This variant has a maximum skeletal muscle PSI of 0.928 and a maximum cardiac muscle PSI of 1.00. The variant was absent in 249174 control chromosomes. c.100186C>T has been reported in the literature in a French family with an autosomal-dominant late onset distal myopathy of the tibial muscular dystrophy phenotype. One homozygous patient in the family was reported with a more severe phenotype (Hackman_2008, Penisson-Besnier_2010). However, genotyping in these studies did not sufficiently rule out other potential causes of skeletal myopathies and segregation of phenotype was not clear. These data indicate that the variant may be associated with disease (at this location, typically dominant tibial muscular dystrophy). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 18948003, 20571043, 19477645). ClinVar contains an entry for this variant (Variation ID: 38440). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
GeneReviews	RCV000031996	SCV000054700	pathologic	Tibial muscular dystrophy	2012-08-23	no assertion criteria provided	curation	Converted during submission to Pathogenic.