Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21916 | 65971;65972;65973 | chr2:178583057;178583056;178583055 | chr2:179447784;179447783;179447782 |
| N2AB | 20275 | 61048;61049;61050 | chr2:178583057;178583056;178583055 | chr2:179447784;179447783;179447782 |
| N2A | 19348 | 58267;58268;58269 | chr2:178583057;178583056;178583055 | chr2:179447784;179447783;179447782 |
| N2B | 12851 | 38776;38777;38778 | chr2:178583057;178583056;178583055 | chr2:179447784;179447783;179447782 |
| Novex-1 | 12976 | 39151;39152;39153 | chr2:178583057;178583056;178583055 | chr2:179447784;179447783;179447782 |
| Novex-2 | 13043 | 39352;39353;39354 | chr2:178583057;178583056;178583055 | chr2:179447784;179447783;179447782 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs148849567  |
0.104 | 0.985 | N | 0.294 | 0.148 | None | gnomAD-2.1.1 | 4.41396E-04 | None | None | None | None | N | None | 4.04605E-03 | 4.00091E-04 | None | 0 | 0 | None | 9.89E-05 | None | 0 | 3.97E-05 | 4.27107E-04 |
| R/Q | rs148849567 |
0.104 | 0.985 | N | 0.294 | 0.148 | None | gnomAD-3.1.2 | 1.25643E-03 | None | None | None | None | N | None | 4.08055E-03 | 1.04849E-03 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 1.43541E-03 |
| R/Q | rs148849567 |
0.104 | 0.985 | N | 0.294 | 0.148 | None | 1000 genomes | 7.98722E-04 | None | None | None | None | N | None | 3E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/Q | rs148849567 |
0.104 | 0.985 | N | 0.294 | 0.148 | None | gnomAD-4.0.0 | 2.58207E-04 | None | None | None | None | N | None | 4.16333E-03 | 6.85756E-04 | None | 3.38341E-05 | 0 | None | 0 | 0 | 3.1399E-05 | 5.50879E-05 | 3.20832E-04 |
| R/W | rs200155485 |
-0.488 | 1.0 | N | 0.271 | 0.344 | None | gnomAD-2.1.1 | 1.14311E-04 | None | None | None | None | N | None | 6.57E-05 | 5.87E-05 | None | 1.80252E-03 | 0 | None | 6.59E-05 | None | 0 | 4.52E-05 | 0 |
| R/W | rs200155485 |
-0.488 | 1.0 | N | 0.271 | 0.344 | None | gnomAD-3.1.2 | 9.87E-05 | None | None | None | None | N | None | 7.25E-05 | 1.96541E-04 | 0 | 1.44009E-03 | 0 | None | 0 | 0 | 5.89E-05 | 0 | 0 |
| R/W | rs200155485 |
-0.488 | 1.0 | N | 0.271 | 0.344 | None | gnomAD-4.0.0 | 6.82838E-05 | None | None | None | None | N | None | 6.68592E-05 | 8.36568E-05 | None | 1.69193E-03 | 0 | None | 0 | 1.64799E-04 | 3.30967E-05 | 3.30535E-05 | 1.1232E-04 |
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 | 0.5847 | likely_pathogenic | 0.5426 | ambiguous | 0.054 | Stabilizing | 0.863 | D | 0.353 | neutral | None | None | None | None | N |
| R/C | 0.3052 | likely_benign | 0.277 | benign | -0.153 | Destabilizing | 0.999 | D | 0.247 | neutral | None | None | None | None | N |
| R/D | 0.6746 | likely_pathogenic | 0.6628 | pathogenic | -0.302 | Destabilizing | 0.884 | D | 0.385 | neutral | None | None | None | None | N |
| R/E | 0.4314 | ambiguous | 0.4244 | ambiguous | -0.267 | Destabilizing | 0.17 | N | 0.212 | neutral | None | None | None | None | N |
| R/F | 0.8068 | likely_pathogenic | 0.7744 | pathogenic | -0.255 | Destabilizing | 0.991 | D | 0.27 | neutral | None | None | None | None | N |
| R/G | 0.2592 | likely_benign | 0.2495 | benign | -0.08 | Destabilizing | 0.983 | D | 0.381 | neutral | N | 0.406755515 | None | None | N |
| R/H | 0.1477 | likely_benign | 0.1328 | benign | -0.571 | Destabilizing | 0.997 | D | 0.275 | neutral | None | None | None | None | N |
| R/I | 0.5546 | ambiguous | 0.5007 | ambiguous | 0.363 | Stabilizing | 0.884 | D | 0.369 | neutral | None | None | None | None | N |
| R/K | 0.1204 | likely_benign | 0.1143 | benign | -0.103 | Destabilizing | 0.079 | N | 0.166 | neutral | None | None | None | None | N |
| R/L | 0.454 | ambiguous | 0.4136 | ambiguous | 0.363 | Stabilizing | 0.858 | D | 0.326 | neutral | N | 0.45001322 | None | None | N |
| R/M | 0.4601 | ambiguous | 0.4204 | ambiguous | -0.037 | Destabilizing | 0.991 | D | 0.295 | neutral | None | None | None | None | N |
| R/N | 0.5881 | likely_pathogenic | 0.5771 | pathogenic | 0.041 | Stabilizing | 0.969 | D | 0.305 | neutral | None | None | None | None | N |
| R/P | 0.6326 | likely_pathogenic | 0.5493 | ambiguous | 0.277 | Stabilizing | 0.998 | D | 0.346 | neutral | N | 0.430926027 | None | None | N |
| R/Q | 0.1342 | likely_benign | 0.1236 | benign | -0.017 | Destabilizing | 0.985 | D | 0.294 | neutral | N | 0.45083994 | None | None | N |
| R/S | 0.6149 | likely_pathogenic | 0.5871 | pathogenic | -0.135 | Destabilizing | 0.939 | D | 0.361 | neutral | None | None | None | None | N |
| R/T | 0.4567 | ambiguous | 0.4255 | ambiguous | None | Stabilizing | 0.939 | D | 0.365 | neutral | None | None | None | None | N |
| R/V | 0.6511 | likely_pathogenic | 0.606 | pathogenic | 0.277 | Stabilizing | 0.17 | N | 0.275 | neutral | None | None | None | None | N |
| R/W | 0.3375 | likely_benign | 0.2955 | benign | -0.436 | Destabilizing | 1.0 | D | 0.271 | neutral | N | 0.512312473 | None | None | N |
| R/Y | 0.5579 | ambiguous | 0.5268 | ambiguous | -0.037 | Destabilizing | 0.997 | D | 0.307 | neutral | None | None | 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.