Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001276345.2(TNNT2):c.294+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,613,882 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
TNNT2 (HGNC:11949): (troponin T2, cardiac type) This gene encodes the cardiac isoform of troponin T. The encoded protein is the tropomyosin-binding subunit of the troponin complex, which is located on the thin filament of striated muscles and regulates muscle contraction in response to alterations in intracellular calcium ion concentration. Mutations in this gene have been associated with familial hypertrophic cardiomyopathy as well as with dilated cardiomyopathy. [provided by RefSeq, May 2022]
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 1-201365603-C-T is Benign according to our data. Variant chr1-201365603-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 36884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-201365603-C-T is described in Lovd as [Benign]. Variant chr1-201365603-C-T is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00976 (1487/152296) while in subpopulation AFR AF= 0.033 (1370/41570). AF 95% confidence interval is 0.0315. There are 24 homozygotes in gnomad4. There are 698 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
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Benign, no assertion criteria provided
clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
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Benign, criteria provided, single submitter
clinical testing
PreventionGenetics, part of Exact Sciences
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Benign, no assertion criteria provided
clinical testing
Clinical Genetics, Academic Medical Center
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Benign, criteria provided, single submitter
clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
May 03, 2010
This variant is not expected to have clinical significance because it is not loc ated in the conserved region of the splicing consensus sequence and it is a comm on variant in the Black population. -
not provided Benign:4
Likely benign, no assertion criteria provided
clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht
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Benign, criteria provided, single submitter
clinical testing
GeneDx
Mar 03, 2015
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Benign, criteria provided, single submitter
clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Jul 21, 2021
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Likely benign, no assertion criteria provided
clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
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Hypertrophic cardiomyopathy Benign:2
Likely benign, criteria provided, single submitter
clinical testing
Illumina Laboratory Services, Illumina
Jun 14, 2016
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Benign, criteria provided, single submitter
clinical testing
Cohesion Phenomics
Oct 10, 2022
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Dilated cardiomyopathy 1D Benign:1
Benign, criteria provided, single submitter
clinical testing
Genome-Nilou Lab
Apr 11, 2023
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Dilated Cardiomyopathy, Dominant Benign:1
Likely benign, criteria provided, single submitter
clinical testing
Illumina Laboratory Services, Illumina
Jun 14, 2016
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Cardiomyopathy, familial restrictive, 3 Benign:1
Benign, criteria provided, single submitter
clinical testing
Genome-Nilou Lab
Apr 11, 2023
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Left ventricular noncompaction cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Feb 22, 2012
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Familial restrictive cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter
clinical testing
Illumina Laboratory Services, Illumina
Jun 14, 2016
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Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter
clinical testing
Ambry Genetics
Dec 18, 2014
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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. -