rs397516479
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BP4BS2
The NM_001276345.2(TNNT2):c.682G>T(p.Val228Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,892 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.
Frequency
Consequence
NM_001276345.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNNT2 | NM_001276345.2 | c.682G>T | p.Val228Leu | missense_variant | 14/17 | ENST00000656932.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNNT2 | ENST00000656932.1 | c.682G>T | p.Val228Leu | missense_variant | 14/17 | NM_001276345.2 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251490Hom.: 1 AF XY: 0.0000221 AC XY: 3AN XY: 135920
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461892Hom.: 1 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727246
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 13, 2013 | proposed classification - variant undergoing re-assessment, contact laboratory - |
Cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Jun 12, 2023 | - - |
Hypertrophic cardiomyopathy Uncertain:1
Uncertain significance, no assertion criteria provided | research | Agnes Ginges Centre for Molecular Cardiology, Centenary Institute | Feb 25, 2020 | TNNT2 Val218Leu has been previously identified in a HCM proband (Walsh R et al., 2017). The variant is present at a low frequency in the Genome Aggregation Database (MAF= 0.00001, http://gnomad.broadinstitute.org/). In silico tools predict the variant to be benign (SIFT, Polyphen-2, MutationTaster). We have identified this variant in a male patient with HCM and no family history of disease (Ingles J, et al, 2017). There is limited evidence to suggest a causative role for this variant, therefore we have classified it as a variant of "uncertain significance". - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at