Submissions for variant NM_001267550.2(TTN):c.43478A>G (p.Glu14493Gly)

gnomAD frequency: 0.00001  dbSNP: rs1316766072

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000997474	SCV001152921	uncertain significance	not provided	2023-07-01	criteria provided, single submitter	clinical testing	TTN: PM2, BP4
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003482157	SCV003934179	uncertain significance	not specified	2023-05-23	criteria provided, single submitter	clinical testing	Variant summary: TTN c.35774A>G (p.Glu11925Gly) results in a non-conservative amino acid change located in the I-band region of the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. 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 4e-06 in 247096 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.35774A>G in individuals affected with 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 uncertain significance.