Submissions for variant NM_001276345.2(TNNT2):c.810+5G>A

gnomAD frequency: 0.00004  dbSNP: rs730881113

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000159318	SCV000209264	uncertain significance	not provided	2021-06-28	criteria provided, single submitter	clinical testing	Identified in a patient with left ventricular hypertrabeculation (LVHT) in the published literature (Miszalski-Jamka et al., 2017); In silico analysis supports a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 28798025, 26582918, 27535533)
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000768714	SCV000900084	uncertain significance	Cardiomyopathy	2015-12-23	criteria provided, single submitter	clinical testing
Invitae	RCV001067013	SCV001232042	uncertain significance	Hypertrophic cardiomyopathy 2; Dilated cardiomyopathy 1D; Cardiomyopathy, familial restrictive, 3	2022-12-06	criteria provided, single submitter	clinical testing	This sequence change falls in intron 14 of the TNNT2 gene. It does not directly change the encoded amino acid sequence of the TNNT2 protein. It affects a nucleotide within the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 181633). This variant is also known as g.201330402C>T. This variant has been observed in individual(s) with TNNT2-related conditions (PMID: 28798025). This variant is present in population databases (rs730881113, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant.
Color Diagnostics, LLC DBA Color Health	RCV000768714	SCV001359846	uncertain significance	Cardiomyopathy	2019-08-11	criteria provided, single submitter	clinical testing	This variant is located in intron 14 of the TNNT2 gene. Computational splicing tools predict that this variant may have a significant impact on RNA splicing. To our knowledge, RNA studies have not been performed for this variant and this variant's impact on the TNNT2 gene function remains unknown. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 7/282664 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics	RCV001067013	SCV002787360	uncertain significance	Hypertrophic cardiomyopathy 2; Dilated cardiomyopathy 1D; Cardiomyopathy, familial restrictive, 3	2022-01-30	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003445594	SCV004173733	uncertain significance	Dilated cardiomyopathy 1D	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003445595	SCV004173734	uncertain significance	Cardiomyopathy, familial restrictive, 3	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003445593	SCV004173735	uncertain significance	Hypertrophic cardiomyopathy 2	2023-04-11	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000768714	SCV004828153	uncertain significance	Cardiomyopathy	2023-05-31	criteria provided, single submitter	clinical testing