Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15758 | 47497;47498;47499 | chr2:178618079;178618078;178618077 | chr2:179482806;179482805;179482804 |
| N2AB | 14117 | 42574;42575;42576 | chr2:178618079;178618078;178618077 | chr2:179482806;179482805;179482804 |
| N2A | 13190 | 39793;39794;39795 | chr2:178618079;178618078;178618077 | chr2:179482806;179482805;179482804 |
| N2B | 6693 | 20302;20303;20304 | chr2:178618079;178618078;178618077 | chr2:179482806;179482805;179482804 |
| Novex-1 | 6818 | 20677;20678;20679 | chr2:178618079;178618078;178618077 | chr2:179482806;179482805;179482804 |
| Novex-2 | 6885 | 20878;20879;20880 | chr2:178618079;178618078;178618077 | chr2:179482806;179482805;179482804 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/G | rs913074596  |
-0.991 | 0.997 | D | 0.682 | 0.444 | 0.740153446146 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | I | None | 0 | 2.92E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/G | rs913074596 |
-0.991 | 0.997 | D | 0.682 | 0.444 | 0.740153446146 | gnomAD-4.0.0 | 1.59549E-06 | None | None | None | None | I | None | 0 | 2.29642E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs2057673756 |
None | 0.944 | N | 0.425 | 0.131 | 0.445007932271 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07211E-04 | 0 |
| V/I | rs2057673756 |
None | 0.944 | N | 0.425 | 0.131 | 0.445007932271 | gnomAD-4.0.0 | 6.58163E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.07211E-04 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3097 | likely_benign | 0.2809 | benign | -0.925 | Destabilizing | 0.944 | D | 0.379 | neutral | N | 0.472698614 | None | None | I |
| V/C | 0.8458 | likely_pathogenic | 0.8054 | pathogenic | -0.813 | Destabilizing | 1.0 | D | 0.596 | neutral | None | None | None | None | I |
| V/D | 0.7117 | likely_pathogenic | 0.7132 | pathogenic | -0.293 | Destabilizing | 0.997 | D | 0.795 | deleterious | D | 0.565415331 | None | None | I |
| V/E | 0.5005 | ambiguous | 0.5049 | ambiguous | -0.374 | Destabilizing | 0.997 | D | 0.733 | deleterious | None | None | None | None | I |
| V/F | 0.3456 | ambiguous | 0.3288 | benign | -0.969 | Destabilizing | 0.999 | D | 0.552 | neutral | D | 0.552597365 | None | None | I |
| V/G | 0.5102 | ambiguous | 0.4835 | ambiguous | -1.114 | Destabilizing | 0.997 | D | 0.682 | prob.neutral | D | 0.565415331 | None | None | I |
| V/H | 0.8077 | likely_pathogenic | 0.7772 | pathogenic | -0.574 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | I |
| V/I | 0.0885 | likely_benign | 0.0844 | benign | -0.555 | Destabilizing | 0.944 | D | 0.425 | neutral | N | 0.476388884 | None | None | I |
| V/K | 0.5211 | ambiguous | 0.5077 | ambiguous | -0.539 | Destabilizing | 0.997 | D | 0.743 | deleterious | None | None | None | None | I |
| V/L | 0.3086 | likely_benign | 0.2593 | benign | -0.555 | Destabilizing | 0.944 | D | 0.351 | neutral | N | 0.463690525 | None | None | I |
| V/M | 0.2377 | likely_benign | 0.2104 | benign | -0.441 | Destabilizing | 0.999 | D | 0.561 | neutral | None | None | None | None | I |
| V/N | 0.5082 | ambiguous | 0.4646 | ambiguous | -0.287 | Destabilizing | 0.997 | D | 0.78 | deleterious | None | None | None | None | I |
| V/P | 0.5939 | likely_pathogenic | 0.5161 | ambiguous | -0.643 | Destabilizing | 0.999 | D | 0.767 | deleterious | None | None | None | None | I |
| V/Q | 0.5069 | ambiguous | 0.4756 | ambiguous | -0.551 | Destabilizing | 0.999 | D | 0.775 | deleterious | None | None | None | None | I |
| V/R | 0.488 | ambiguous | 0.4838 | ambiguous | -0.033 | Destabilizing | 0.997 | D | 0.812 | deleterious | None | None | None | None | I |
| V/S | 0.4128 | ambiguous | 0.3678 | ambiguous | -0.811 | Destabilizing | 0.99 | D | 0.566 | neutral | None | None | None | None | I |
| V/T | 0.2595 | likely_benign | 0.2354 | benign | -0.787 | Destabilizing | 0.422 | N | 0.191 | neutral | None | None | None | None | I |
| V/W | 0.9474 | likely_pathogenic | 0.9401 | pathogenic | -0.995 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | I |
| V/Y | 0.768 | likely_pathogenic | 0.7415 | pathogenic | -0.7 | Destabilizing | 0.999 | D | 0.554 | neutral | None | None | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.