Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13840 | 41743;41744;41745 | chr2:178636053;178636052;178636051 | chr2:179500780;179500779;179500778 |
| N2AB | 12199 | 36820;36821;36822 | chr2:178636053;178636052;178636051 | chr2:179500780;179500779;179500778 |
| N2A | 11272 | 34039;34040;34041 | chr2:178636053;178636052;178636051 | chr2:179500780;179500779;179500778 |
| N2B | 4775 | 14548;14549;14550 | chr2:178636053;178636052;178636051 | chr2:179500780;179500779;179500778 |
| Novex-1 | 4900 | 14923;14924;14925 | chr2:178636053;178636052;178636051 | chr2:179500780;179500779;179500778 |
| Novex-2 | 4967 | 15124;15125;15126 | chr2:178636053;178636052;178636051 | chr2:179500780;179500779;179500778 |
| 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/S | rs760261561  |
-0.352 | 0.27 | N | 0.206 | 0.094 | 0.0716867268079 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| N/S | rs760261561 |
-0.352 | 0.27 | N | 0.206 | 0.094 | 0.0716867268079 | gnomAD-4.0.0 | 6.84398E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99649E-06 | 0 | 0 |
| N/Y | rs763460143 |
-0.376 | 0.927 | N | 0.528 | 0.179 | 0.243972157842 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| N/Y | rs763460143 |
-0.376 | 0.927 | N | 0.528 | 0.179 | 0.243972157842 | gnomAD-4.0.0 | 1.5923E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43328E-05 | 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 | 0.2569 | likely_benign | 0.2431 | benign | -0.713 | Destabilizing | 0.329 | N | 0.287 | neutral | None | None | None | None | N |
| N/C | 0.3514 | ambiguous | 0.3314 | benign | 0.083 | Stabilizing | 0.995 | D | 0.385 | neutral | None | None | None | None | N |
| N/D | 0.2478 | likely_benign | 0.2943 | benign | -0.793 | Destabilizing | 0.425 | N | 0.198 | neutral | N | 0.342091659 | None | None | N |
| N/E | 0.4855 | ambiguous | 0.5367 | ambiguous | -0.706 | Destabilizing | 0.329 | N | 0.162 | neutral | None | None | None | None | N |
| N/F | 0.5593 | ambiguous | 0.5653 | pathogenic | -0.497 | Destabilizing | 0.893 | D | 0.561 | neutral | None | None | None | None | N |
| N/G | 0.3403 | ambiguous | 0.3281 | benign | -1.05 | Destabilizing | 0.495 | N | 0.14 | neutral | None | None | None | None | N |
| N/H | 0.1427 | likely_benign | 0.1589 | benign | -0.903 | Destabilizing | 0.927 | D | 0.375 | neutral | N | 0.34727442 | None | None | N |
| N/I | 0.2449 | likely_benign | 0.2591 | benign | 0.139 | Stabilizing | 0.473 | N | 0.473 | neutral | N | 0.349891741 | None | None | N |
| N/K | 0.4072 | ambiguous | 0.4864 | ambiguous | -0.301 | Destabilizing | 0.485 | N | 0.133 | neutral | N | 0.338861755 | None | None | N |
| N/L | 0.234 | likely_benign | 0.2119 | benign | 0.139 | Stabilizing | 0.144 | N | 0.325 | neutral | None | None | None | None | N |
| N/M | 0.3225 | likely_benign | 0.2993 | benign | 0.644 | Stabilizing | 0.085 | N | 0.295 | neutral | None | None | None | None | N |
| N/P | 0.5817 | likely_pathogenic | 0.5785 | pathogenic | -0.115 | Destabilizing | 0.828 | D | 0.46 | neutral | None | None | None | None | N |
| N/Q | 0.3977 | ambiguous | 0.4117 | ambiguous | -0.919 | Destabilizing | 0.013 | N | 0.033 | neutral | None | None | None | None | N |
| N/R | 0.4088 | ambiguous | 0.4802 | ambiguous | -0.337 | Destabilizing | 0.704 | D | 0.205 | neutral | None | None | None | None | N |
| N/S | 0.0754 | likely_benign | 0.0687 | benign | -0.849 | Destabilizing | 0.27 | N | 0.206 | neutral | N | 0.333589128 | None | None | N |
| N/T | 0.1275 | likely_benign | 0.1175 | benign | -0.581 | Destabilizing | 0.01 | N | 0.053 | neutral | N | 0.330863286 | None | None | N |
| N/V | 0.2617 | likely_benign | 0.2632 | benign | -0.115 | Destabilizing | 0.329 | N | 0.297 | neutral | None | None | None | None | N |
| N/W | 0.7948 | likely_pathogenic | 0.8051 | pathogenic | -0.302 | Destabilizing | 0.995 | D | 0.405 | neutral | None | None | None | None | N |
| N/Y | 0.1931 | likely_benign | 0.2088 | benign | -0.077 | Destabilizing | 0.927 | D | 0.528 | neutral | N | 0.343180013 | 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.