chr1-201363323-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3
The NM_001276345.2(TNNT2):c.573G>T(p.Met191Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M191T) has been classified as Uncertain significance.
Frequency
Consequence
NM_001276345.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNNT2 | NM_001276345.2 | c.573G>T | p.Met191Ile | missense_variant | 12/17 | ENST00000656932.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNNT2 | ENST00000656932.1 | c.573G>T | p.Met191Ile | missense_variant | 12/17 | NM_001276345.2 | A2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
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 | Feb 16, 2015 | Variant classified as Uncertain Significance - Favor Pathogenic. The p.Met181Ile variant in TNNT2 has not been previously reported in individuals with cardiomyo pathy and was absent from large population studies. This variant was predicted t o be pathogenic using a computational tool clinically validated by our laborator y. This tool's pathogenic prediction is estimated to be correct 94% of the time (Jordan 2011). In summary, while there is some suspicion for a pathogenic role, the clinical significance of the p.Met181Ile variant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at