rs4523540
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM5
The NM_001276345.2(TNNT2):c.835A>T(p.Asn279Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N279D) has been classified as Uncertain significance.
Frequency
Consequence
NM_001276345.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNNT2 | NM_001276345.2 | c.835A>T | p.Asn279Tyr | missense_variant | 16/17 | ENST00000656932.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNNT2 | ENST00000656932.1 | c.835A>T | p.Asn279Tyr | missense_variant | 16/17 | NM_001276345.2 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 21, 2011 | This variant is denoted Asn269Tyr (aka N269Y) at the protein level and c.805 A>T at the cDNA level. Asn269Tyr results in a conservative substitution of one neutral, polar amino acid for another at a residue that is conserved across mammal species, but the Asn269 residue is not conserved in lower species. However, mutations in nearby codons (Asn262Ser, Asp270Asn, Asn271Ile) have been reported in association with cardiomyopathy, supporting the functional importance of this region of the protein. In summary, with the clinical and molecular information available at this time, we cannot unequivocally determine whether the Asn269Tyr variant is a disease-causing mutation or a rare benign variant. The variant is found in DCM panel(s). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at