ClinVar Miner

Submissions for variant NM_001276345.2(TNNT2):c.691A>G (p.Ile231Val)

gnomAD frequency: 0.00003  dbSNP: rs886045828
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000374831 SCV000353332 uncertain significance Familial restrictive cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000280335 SCV000353333 uncertain significance Hypertrophic cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000335373 SCV000353334 uncertain significance Left ventricular noncompaction cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000406090 SCV000353335 uncertain significance Dilated Cardiomyopathy, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000695810 SCV000824331 uncertain significance Hypertrophic cardiomyopathy 2; Dilated cardiomyopathy 1D; Cardiomyopathy, familial restrictive, 3 2023-06-05 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TNNT2 protein function. ClinVar contains an entry for this variant (Variation ID: 294895). This variant has not been reported in the literature in individuals affected with TNNT2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.02%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 221 of the TNNT2 protein (p.Ile221Val).
Ambry Genetics RCV003380542 SCV004091382 uncertain significance Cardiovascular phenotype 2023-06-23 criteria provided, single submitter clinical testing The p.I221V variant (also known as c.661A>G), located in coding exon 12 of the TNNT2 gene, results from an A to G substitution at nucleotide position 661. The isoleucine at codon 221 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV003449018 SCV004181254 uncertain significance Dilated cardiomyopathy 1D 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003449019 SCV004181255 uncertain significance Cardiomyopathy, familial restrictive, 3 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003449017 SCV004181256 uncertain significance Hypertrophic cardiomyopathy 2 2023-04-11 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV003532080 SCV004359928 uncertain significance Cardiomyopathy 2023-01-23 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 221 of the TNNT2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TNNT2-related disorders in the literature. This variant has been identified in 2/31394 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The 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.

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