Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29602 | 89029;89030;89031 | chr2:178554543;178554542;178554541 | chr2:179419270;179419269;179419268 |
| N2AB | 27961 | 84106;84107;84108 | chr2:178554543;178554542;178554541 | chr2:179419270;179419269;179419268 |
| N2A | 27034 | 81325;81326;81327 | chr2:178554543;178554542;178554541 | chr2:179419270;179419269;179419268 |
| N2B | 20537 | 61834;61835;61836 | chr2:178554543;178554542;178554541 | chr2:179419270;179419269;179419268 |
| Novex-1 | 20662 | 62209;62210;62211 | chr2:178554543;178554542;178554541 | chr2:179419270;179419269;179419268 |
| Novex-2 | 20729 | 62410;62411;62412 | chr2:178554543;178554542;178554541 | chr2:179419270;179419269;179419268 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/K | rs1700590955  |
None | 1.0 | N | 0.661 | 0.334 | 0.1749357433 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| N/S | rs749229315 |
-0.818 | 0.999 | N | 0.47 | 0.39 | 0.173771789658 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| N/S | rs749229315 |
-0.818 | 0.999 | N | 0.47 | 0.39 | 0.173771789658 | gnomAD-4.0.0 | 1.59123E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85785E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.8653 | likely_pathogenic | 0.8628 | pathogenic | -0.934 | Destabilizing | 1.0 | D | 0.656 | neutral | None | None | None | None | N |
| N/C | 0.6846 | likely_pathogenic | 0.6653 | pathogenic | -0.065 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| N/D | 0.875 | likely_pathogenic | 0.8489 | pathogenic | -0.45 | Destabilizing | 0.999 | D | 0.537 | neutral | N | 0.48534521 | None | None | N |
| N/E | 0.9599 | likely_pathogenic | 0.9501 | pathogenic | -0.342 | Destabilizing | 0.999 | D | 0.637 | neutral | None | None | None | None | N |
| N/F | 0.962 | likely_pathogenic | 0.963 | pathogenic | -0.615 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| N/G | 0.8175 | likely_pathogenic | 0.8267 | pathogenic | -1.285 | Destabilizing | 0.999 | D | 0.456 | neutral | None | None | None | None | N |
| N/H | 0.4512 | ambiguous | 0.4571 | ambiguous | -0.912 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | N | 0.472285152 | None | None | N |
| N/I | 0.8995 | likely_pathogenic | 0.8875 | pathogenic | -0.036 | Destabilizing | 1.0 | D | 0.669 | neutral | N | 0.469215964 | None | None | N |
| N/K | 0.9442 | likely_pathogenic | 0.933 | pathogenic | -0.303 | Destabilizing | 1.0 | D | 0.661 | neutral | N | 0.477266897 | None | None | N |
| N/L | 0.8636 | likely_pathogenic | 0.8586 | pathogenic | -0.036 | Destabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | N |
| N/M | 0.8933 | likely_pathogenic | 0.8866 | pathogenic | 0.33 | Stabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | N |
| N/P | 0.9878 | likely_pathogenic | 0.9881 | pathogenic | -0.306 | Destabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | N |
| N/Q | 0.8909 | likely_pathogenic | 0.8821 | pathogenic | -0.857 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| N/R | 0.9117 | likely_pathogenic | 0.9015 | pathogenic | -0.326 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| N/S | 0.3239 | likely_benign | 0.3213 | benign | -0.967 | Destabilizing | 0.999 | D | 0.47 | neutral | N | 0.484923589 | None | None | N |
| N/T | 0.7788 | likely_pathogenic | 0.7516 | pathogenic | -0.661 | Destabilizing | 0.999 | D | 0.632 | neutral | N | 0.454421749 | None | None | N |
| N/V | 0.8758 | likely_pathogenic | 0.8587 | pathogenic | -0.306 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| N/W | 0.9814 | likely_pathogenic | 0.9818 | pathogenic | -0.357 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | N |
| N/Y | 0.7511 | likely_pathogenic | 0.7287 | pathogenic | -0.163 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | N | 0.492435554 | None | None | N |
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.