Submissions for variant NM_000363.5(TNNI3):c.12-7del

dbSNP: rs370714315

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036269	SCV000059921	likely benign	not specified	2012-08-01	criteria provided, single submitter	clinical testing	12-7delC in intron 1 of TNNI3: This variant is unlikely to have clinical signifi cance because it is not located within the conserved splice consensus sequence. In addition, there are no reports of disease-causing splicing variants in the TN NI3 gene. Of note, the variant has been detected by our laboratory in 5 individu als with various cardiomyopathies (HCM or LVNC), 4 of whom were of confirmed Bla ck ancestry. This raises the possibility that this variant is common in the Bla ck population. A modifying effect cannot be excluded.
GeneDx	RCV000159208	SCV000209154	benign	Cardiomyopathy	2012-07-26	criteria provided, single submitter	clinical testing	The variant is found in DCM panel(s).
Eurofins Ntd Llc (ga)	RCV000036269	SCV000227105	benign	not specified	2015-04-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000232527	SCV000284651	benign	Hypertrophic cardiomyopathy	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000297174	SCV000414777	uncertain significance	Familial Hypertrophic Cardiomyopathy with Wolff-Parkinson-White Syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000356727	SCV000414778	uncertain significance	Familial restrictive cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000263491	SCV000414779	uncertain significance	Dilated Cardiomyopathy, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000232527	SCV000414780	uncertain significance	Hypertrophic cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000036269	SCV000920308	benign	not specified	2017-09-05	criteria provided, single submitter	clinical testing	Variant summary: The TNNI3 c.12-7delC variant involves the alteration of a non-conserved intronic nucleotide. MutationTaster predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 52/108562 control chromosomes from all ethnicities, but was predominantly observed in the African subpopulation at a frequency of 0.005965 (50/8382). This frequency is about 48 times the estimated maximal expected allele frequency of a pathogenic TNNI3 variant (0.000125), strongly suggesting this is likely a benign polymorphism found primarily in populations of African origin. In addition, nn an internal LCA sample, the variant was found to co-occur with a pathogenic DSP mutation (c.1dupA), suggesting the variant is not responsible for disease in this individual. Multiple clinical diagnostic laboratories/reputable databases have classified this variant with differing interpretations, including uncertain significance, likely benign, and benign, with a classification of benign being the most recent. Taken together, this variant is classified as benign.
Mendelics	RCV000991061	SCV001142166	benign	Hypertrophic cardiomyopathy 1	2019-05-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000159208	SCV001355396	benign	Cardiomyopathy	2019-11-21	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000036269	SCV001924816	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000036269	SCV001972526	benign	not specified		no assertion criteria provided	clinical testing