Submissions for variant NM_001267550.2(TTN):c.105787_105788delinsTT (p.Ala35263Phe)

dbSNP: rs794729250

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000184182	SCV000236802	likely benign	not provided	2012-09-26	criteria provided, single submitter	clinical testing	The variant is found in DCM panel(s).
Invitae	RCV001081444	SCV000286412	benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-31	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000254386	SCV000315659	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000252028	SCV000318055	likely benign	Cardiovascular phenotype	2012-11-28	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Athena Diagnostics Inc	RCV000254386	SCV000844607	benign	not specified	2019-11-05	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000254386	SCV001362592	benign	not specified	2019-08-26	criteria provided, single submitter	clinical testing	Variant summary: TTN c.98083_98084delinsTT (p.Ala32695Phe) results in a non-conservative amino acid change in the encoded protein sequence. Two of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.011 in 280436 control chromosomes in the gnomAD database, including 25 homozygotes. The observed variant frequency is approximately 18 fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Cardiomyopathy phenotype (0.00063), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.98083_98084delinsTT in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and all of them classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798645	SCV002042341	likely benign	Cardiomyopathy	2023-01-12	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001840303	SCV002100643	benign	Autosomal recessive limb-girdle muscular dystrophy type 2J	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001840304	SCV002100654	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001840305	SCV002100665	benign	Early-onset myopathy with fatal cardiomyopathy	2021-09-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001840302	SCV002100676	benign	Tibial muscular dystrophy	2021-09-10	criteria provided, single submitter	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000254386	SCV001955053	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000254386	SCV001969411	benign	not specified		no assertion criteria provided	clinical testing