Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3425 | 10498;10499;10500 | chr2:178759014;178759013;178759012 | chr2:179623741;179623740;179623739 |
| N2AB | 3425 | 10498;10499;10500 | chr2:178759014;178759013;178759012 | chr2:179623741;179623740;179623739 |
| N2A | 3425 | 10498;10499;10500 | chr2:178759014;178759013;178759012 | chr2:179623741;179623740;179623739 |
| N2B | 3379 | 10360;10361;10362 | chr2:178759014;178759013;178759012 | chr2:179623741;179623740;179623739 |
| Novex-1 | 3379 | 10360;10361;10362 | chr2:178759014;178759013;178759012 | chr2:179623741;179623740;179623739 |
| Novex-2 | 3379 | 10360;10361;10362 | chr2:178759014;178759013;178759012 | chr2:179623741;179623740;179623739 |
| Novex-3 | 3425 | 10498;10499;10500 | chr2:178759014;178759013;178759012 | chr2:179623741;179623740;179623739 |
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/E | None | None | 0.998 | N | 0.71 | 0.561 | 0.85112795881 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 1.01626E-03 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs879184037  |
None | 0.987 | N | 0.521 | 0.374 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/I | rs879184037 |
None | 0.987 | N | 0.521 | 0.374 | None | gnomAD-4.0.0 | 3.84228E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.17638E-06 | 0 | 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 | 0.2094 | likely_benign | 0.2665 | benign | -1.117 | Destabilizing | 0.333 | N | 0.221 | neutral | N | 0.474812306 | None | None | I |
| V/C | 0.8953 | likely_pathogenic | 0.8938 | pathogenic | -0.931 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | I |
| V/D | 0.5924 | likely_pathogenic | 0.6788 | pathogenic | -0.574 | Destabilizing | 0.999 | D | 0.784 | deleterious | None | None | None | None | I |
| V/E | 0.4945 | ambiguous | 0.5663 | pathogenic | -0.566 | Destabilizing | 0.998 | D | 0.71 | prob.delet. | N | 0.513118459 | None | None | I |
| V/F | 0.3772 | ambiguous | 0.3991 | ambiguous | -0.737 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | I |
| V/G | 0.3913 | ambiguous | 0.4523 | ambiguous | -1.425 | Destabilizing | 0.989 | D | 0.722 | prob.delet. | D | 0.581492115 | None | None | I |
| V/H | 0.8505 | likely_pathogenic | 0.8755 | pathogenic | -0.842 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | I |
| V/I | 0.1069 | likely_benign | 0.1181 | benign | -0.383 | Destabilizing | 0.987 | D | 0.521 | neutral | N | 0.514886931 | None | None | I |
| V/K | 0.6492 | likely_pathogenic | 0.6907 | pathogenic | -0.908 | Destabilizing | 0.999 | D | 0.73 | prob.delet. | None | None | None | None | I |
| V/L | 0.4055 | ambiguous | 0.4882 | ambiguous | -0.383 | Destabilizing | 0.973 | D | 0.553 | neutral | D | 0.555283286 | None | None | I |
| V/M | 0.2935 | likely_benign | 0.3271 | benign | -0.452 | Destabilizing | 1.0 | D | 0.646 | neutral | None | None | None | None | I |
| V/N | 0.566 | likely_pathogenic | 0.643 | pathogenic | -0.799 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | I |
| V/P | 0.984 | likely_pathogenic | 0.9867 | pathogenic | -0.591 | Destabilizing | 0.999 | D | 0.763 | deleterious | None | None | None | None | I |
| V/Q | 0.6103 | likely_pathogenic | 0.6575 | pathogenic | -0.911 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | I |
| V/R | 0.6358 | likely_pathogenic | 0.6518 | pathogenic | -0.466 | Destabilizing | 0.999 | D | 0.795 | deleterious | None | None | None | None | I |
| V/S | 0.3573 | ambiguous | 0.4518 | ambiguous | -1.371 | Destabilizing | 0.983 | D | 0.673 | neutral | None | None | None | None | I |
| V/T | 0.2573 | likely_benign | 0.345 | ambiguous | -1.242 | Destabilizing | 0.992 | D | 0.554 | neutral | None | None | None | None | I |
| V/W | 0.9625 | likely_pathogenic | 0.9624 | pathogenic | -0.9 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| V/Y | 0.8024 | likely_pathogenic | 0.8115 | pathogenic | -0.586 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | 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.