2-178774420-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_001267550.2(TTN):āc.6844T>Cā(p.Tyr2282His) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y2282S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.6844T>C | p.Tyr2282His | missense_variant | 30/363 | ENST00000589042.5 | |
TTN | NM_133379.5 | c.6844T>C | p.Tyr2282His | missense_variant | 30/46 | ENST00000360870.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.6844T>C | p.Tyr2282His | missense_variant | 30/363 | 5 | NM_001267550.2 | P1 | |
TTN | ENST00000360870.10 | c.6844T>C | p.Tyr2282His | missense_variant | 30/46 | 5 | NM_133379.5 | ||
TTN-AS1 | ENST00000659121.1 | n.1847A>G | non_coding_transcript_exon_variant | 12/13 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152224Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461290Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 726986
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74358
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 | Aug 22, 2013 | Variant classified as Uncertain Significance - Favor Benign. The Tyr2282His vari ant in TTN has not been reported in individuals with cardiomyopathy or in large population studies. Tyrosine (Tyr) at position 2282 is not conserved among mamma ls or evolutionarily distant species, which suggests that a change at this posit ion may be tolerated. Additional computational analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. While the lack of conservation across many sp ecies suggests that this variant is more likely benign, additional information i s needed to fully assess its clinical significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at