Submissions for variant NM_001267550.2(TTN):c.7783A>G (p.Met2595Val)

gnomAD frequency: 0.00001  dbSNP: rs760786665

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000501863	SCV000597708	uncertain significance	not specified	2017-02-08	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001170101	SCV001332640	uncertain significance	Cardiomyopathy	2018-03-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001541554	SCV001759568	likely benign	not provided	2020-02-21	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000501863	SCV004020313	uncertain significance	not specified	2023-06-26	criteria provided, single submitter	clinical testing	Variant summary: TTN c.7783A>G (p.Met2595Val) results in a conservative amino acid change located in the I-band region of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 (i.e., 6 heterozygotes) in 250362 control chromosomes (gnomAD v2.1, Exomes dataset). 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.7783A>G in individuals affected with Limb-Girdle Muscular Dystrophy, Type 2J and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have reported clinical-significance assessments for this variant to ClinVar after 2014 with conflicting assessments: two submitters classified the variant as uncertain significance, and one submitter classified it as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.