Submissions for variant NM_001267550.2(TTN):c.107780_107790delinsTGAAAGAAAAA (p.Glu35927_Trp35930delinsValLysGluLys)

dbSNP: rs281864927

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000406890	SCV000340098	pathogenic	not provided	2018-09-11	criteria provided, single submitter	clinical testing
Invitae	RCV000700718	SCV000829486	pathogenic	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2022-09-04	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant is located in the M band of TTN (PMID: 25589632). Variants in this region may be relevant for neuromuscular disorders, but have not been definitively shown to cause cardiomyopathy (PMID: 23975875). Experimental studies have shown that this variant affects TTN function (PMID: 24395473, 25589632, 25739468). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. This variant has been observed in individuals with autosomal dominant tibial muscular dystrophy and autosomal recessive limb-girdle muscular dystrophy in many families (PMID: 12145747, 15728284, 24395473). It is commonly reported in individuals of Finnish ancestry (PMID: 12145747, 15728284, 24395473). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant, c.107780_107790delinsTGAAAGAAAAA, is a complex sequence change that results in the deletion of 4 and insertion of 4 amino acid(s) in the TTN protein (p.Glu35927_Trp35930delinsValLysGluLys).
Blueprint Genetics	RCV000406890	SCV000927484	pathogenic	not provided	2017-11-29	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000406890	SCV001146312	pathogenic	not provided	2018-12-24	criteria provided, single submitter	clinical testing	Not found in the total gnomAD dataset, and the data is high quality (0/248952 chr). Found in at least one symptomatic patient. Statistically associated with disease in multiple families. (p < 0.05)
Fulgent Genetics, Fulgent Genetics	RCV002496344	SCV002804490	pathogenic	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9	2021-07-21	criteria provided, single submitter	clinical testing
Genetics and Personalized Medicine Clinic, Tartu University Hospital	RCV000013488	SCV004228503	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2J		criteria provided, single submitter	clinical testing	We found in compound heterozygous state in trans with splicing variant NM_001267550.2(TTN):c.64672+2dup in two patients with Titin-related limb-girdle muscular dystrophy R10 and in monoallelic state in family members with tibial muscular dystrophy.
OMIM	RCV000013487	SCV000033734	pathogenic	Tibial muscular dystrophy	2010-09-24	no assertion criteria provided	literature only
GeneReviews	RCV000013487	SCV000054695	not provided	Tibial muscular dystrophy		no assertion provided	literature only
OMIM	RCV000013488	SCV000809049	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2J	2010-09-24	no assertion criteria provided	literature only