Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2540 | 7843;7844;7845 | chr2:178773346;178773345;178773344 | chr2:179638073;179638072;179638071 |
| N2AB | 2540 | 7843;7844;7845 | chr2:178773346;178773345;178773344 | chr2:179638073;179638072;179638071 |
| N2A | 2540 | 7843;7844;7845 | chr2:178773346;178773345;178773344 | chr2:179638073;179638072;179638071 |
| N2B | 2494 | 7705;7706;7707 | chr2:178773346;178773345;178773344 | chr2:179638073;179638072;179638071 |
| Novex-1 | 2494 | 7705;7706;7707 | chr2:178773346;178773345;178773344 | chr2:179638073;179638072;179638071 |
| Novex-2 | 2494 | 7705;7706;7707 | chr2:178773346;178773345;178773344 | chr2:179638073;179638072;179638071 |
| Novex-3 | 2540 | 7843;7844;7845 | chr2:178773346;178773345;178773344 | chr2:179638073;179638072;179638071 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs368574470  |
-0.142 | 0.99 | N | 0.279 | 0.229 | None | gnomAD-2.1.1 | 5.69E-05 | None | None | None | None | I | None | 2.4665E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.01E-05 | 1.39743E-04 |
| R/C | rs368574470 |
-0.142 | 0.99 | N | 0.279 | 0.229 | None | gnomAD-3.1.2 | 1.05187E-04 | None | None | None | None | I | None | 2.17244E-04 | 0 | 0 | 0 | 1.9253E-04 | None | 0 | 0 | 8.82E-05 | 0 | 0 |
| R/C | rs368574470 |
-0.142 | 0.99 | N | 0.279 | 0.229 | None | gnomAD-4.0.0 | 1.00996E-04 | None | None | None | None | I | None | 2.66581E-04 | 1.66694E-05 | None | 0 | 2.23095E-05 | None | 0 | 0 | 1.1526E-04 | 0 | 8E-05 |
| R/H | None | -0.575 | 0.002 | N | 0.181 | 0.162 | None | gnomAD-2.1.1 | 4E-05 | None | None | None | None | I | None | 0 | 1.15902E-04 | None | 0 | 1.09182E-04 | None | 0 | None | 0 | 3.54E-05 | 0 |
| R/H | None | -0.575 | 0.002 | N | 0.181 | 0.162 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 5.78704E-04 | None | 0 | 0 | 4.41E-05 | 0 | 4.78011E-04 |
| R/H | None | -0.575 | 0.002 | N | 0.181 | 0.162 | None | gnomAD-4.0.0 | 1.22078E-04 | None | None | None | None | I | None | 1.33615E-05 | 6.67022E-05 | None | 0 | 3.14536E-03 | None | 0 | 3.28947E-04 | 3.64415E-05 | 2.1966E-05 | 6.40266E-05 |
| R/P | rs397517725 |
0.15 | 0.523 | N | 0.452 | 0.321 | 0.0762999501168 | gnomAD-2.1.1 | 4E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.84E-06 | 0 |
| R/P | rs397517725 |
0.15 | 0.523 | N | 0.452 | 0.321 | 0.0762999501168 | gnomAD-4.0.0 | 3.42065E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59727E-06 | 0 | 1.65612E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.2246 | likely_benign | 0.2253 | benign | 0.057 | Stabilizing | 0.025 | N | 0.269 | neutral | None | None | None | None | I |
| R/C | 0.1191 | likely_benign | 0.1181 | benign | -0.252 | Destabilizing | 0.99 | D | 0.279 | neutral | N | 0.508310303 | None | None | I |
| R/D | 0.2966 | likely_benign | 0.2988 | benign | -0.236 | Destabilizing | 0.055 | N | 0.295 | neutral | None | None | None | None | I |
| R/E | 0.1791 | likely_benign | 0.1861 | benign | -0.18 | Destabilizing | 0.001 | N | 0.139 | neutral | None | None | None | None | I |
| R/F | 0.4091 | ambiguous | 0.4148 | ambiguous | -0.234 | Destabilizing | 0.497 | N | 0.387 | neutral | None | None | None | None | I |
| R/G | 0.1468 | likely_benign | 0.154 | benign | -0.108 | Destabilizing | 0.182 | N | 0.305 | neutral | N | 0.506613924 | None | None | I |
| R/H | 0.0675 | likely_benign | 0.0687 | benign | -0.631 | Destabilizing | 0.002 | N | 0.181 | neutral | N | 0.448147861 | None | None | I |
| R/I | 0.2485 | likely_benign | 0.2274 | benign | 0.448 | Stabilizing | 0.667 | D | 0.429 | neutral | None | None | None | None | I |
| R/K | 0.0797 | likely_benign | 0.0874 | benign | -0.13 | Destabilizing | None | N | 0.157 | neutral | None | None | None | None | I |
| R/L | 0.1782 | likely_benign | 0.1788 | benign | 0.448 | Stabilizing | 0.182 | N | 0.333 | neutral | N | 0.514622634 | None | None | I |
| R/M | 0.2598 | likely_benign | 0.2547 | benign | -0.044 | Destabilizing | 0.667 | D | 0.333 | neutral | None | None | None | None | I |
| R/N | 0.2237 | likely_benign | 0.2263 | benign | -0.055 | Destabilizing | 0.055 | N | 0.341 | neutral | None | None | None | None | I |
| R/P | 0.4196 | ambiguous | 0.4318 | ambiguous | 0.337 | Stabilizing | 0.523 | D | 0.452 | neutral | N | 0.49357741 | None | None | I |
| R/Q | 0.0771 | likely_benign | 0.0807 | benign | -0.086 | Destabilizing | 0.002 | N | 0.196 | neutral | None | None | None | None | I |
| R/S | 0.2124 | likely_benign | 0.2104 | benign | -0.274 | Destabilizing | 0.1 | N | 0.313 | neutral | N | 0.496373883 | None | None | I |
| R/T | 0.1428 | likely_benign | 0.1377 | benign | -0.096 | Destabilizing | 0.104 | N | 0.352 | neutral | None | None | None | None | I |
| R/V | 0.2637 | likely_benign | 0.2596 | benign | 0.337 | Stabilizing | 0.22 | N | 0.437 | neutral | None | None | None | None | I |
| R/W | 0.1681 | likely_benign | 0.1631 | benign | -0.389 | Destabilizing | 0.958 | D | 0.281 | neutral | None | None | None | None | I |
| R/Y | 0.23 | likely_benign | 0.2409 | benign | 0.032 | Stabilizing | 0.124 | N | 0.459 | 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.