Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28246 | 84961;84962;84963 | chr2:178561396;178561395;178561394 | chr2:179426123;179426122;179426121 |
| N2AB | 26605 | 80038;80039;80040 | chr2:178561396;178561395;178561394 | chr2:179426123;179426122;179426121 |
| N2A | 25678 | 77257;77258;77259 | chr2:178561396;178561395;178561394 | chr2:179426123;179426122;179426121 |
| N2B | 19181 | 57766;57767;57768 | chr2:178561396;178561395;178561394 | chr2:179426123;179426122;179426121 |
| Novex-1 | 19306 | 58141;58142;58143 | chr2:178561396;178561395;178561394 | chr2:179426123;179426122;179426121 |
| Novex-2 | 19373 | 58342;58343;58344 | chr2:178561396;178561395;178561394 | chr2:179426123;179426122;179426121 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs755762249  |
-0.414 | 0.993 | N | 0.677 | 0.33 | 0.405979908929 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| P/L | rs755762249 |
-0.414 | 0.993 | N | 0.677 | 0.33 | 0.405979908929 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/L | rs755762249 |
-0.414 | 0.993 | N | 0.677 | 0.33 | 0.405979908929 | gnomAD-4.0.0 | 2.47892E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39043E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0685 | likely_benign | 0.0613 | benign | -1.217 | Destabilizing | 0.355 | N | 0.304 | neutral | N | 0.516897147 | None | None | N |
| P/C | 0.5086 | ambiguous | 0.468 | ambiguous | -0.531 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| P/D | 0.8097 | likely_pathogenic | 0.7717 | pathogenic | -1.333 | Destabilizing | 0.965 | D | 0.632 | neutral | None | None | None | None | N |
| P/E | 0.6426 | likely_pathogenic | 0.5839 | pathogenic | -1.404 | Destabilizing | 0.628 | D | 0.329 | neutral | None | None | None | None | N |
| P/F | 0.5405 | ambiguous | 0.5108 | ambiguous | -1.18 | Destabilizing | 1.0 | D | 0.703 | prob.delet. | None | None | None | None | N |
| P/G | 0.3579 | ambiguous | 0.3257 | benign | -1.448 | Destabilizing | 0.982 | D | 0.625 | neutral | None | None | None | None | N |
| P/H | 0.4289 | ambiguous | 0.4008 | ambiguous | -1.114 | Destabilizing | 1.0 | D | 0.652 | prob.neutral | None | None | None | None | N |
| P/I | 0.4033 | ambiguous | 0.3838 | ambiguous | -0.706 | Destabilizing | 0.997 | D | 0.749 | deleterious | None | None | None | None | N |
| P/K | 0.7319 | likely_pathogenic | 0.6877 | pathogenic | -1.099 | Destabilizing | 0.982 | D | 0.645 | neutral | None | None | None | None | N |
| P/L | 0.2139 | likely_benign | 0.1958 | benign | -0.706 | Destabilizing | 0.993 | D | 0.677 | prob.neutral | N | 0.46935996 | None | None | N |
| P/M | 0.3694 | ambiguous | 0.3443 | ambiguous | -0.389 | Destabilizing | 1.0 | D | 0.656 | prob.neutral | None | None | None | None | N |
| P/N | 0.576 | likely_pathogenic | 0.5326 | ambiguous | -0.67 | Destabilizing | 0.997 | D | 0.7 | prob.delet. | None | None | None | None | N |
| P/Q | 0.4078 | ambiguous | 0.3659 | ambiguous | -0.94 | Destabilizing | 0.993 | D | 0.623 | neutral | N | 0.494202619 | None | None | N |
| P/R | 0.5663 | likely_pathogenic | 0.512 | ambiguous | -0.483 | Destabilizing | 0.993 | D | 0.704 | prob.delet. | N | 0.494202619 | None | None | N |
| P/S | 0.1807 | likely_benign | 0.1638 | benign | -1.001 | Destabilizing | 0.954 | D | 0.593 | neutral | N | 0.467602441 | None | None | N |
| P/T | 0.171 | likely_benign | 0.1484 | benign | -0.987 | Destabilizing | 0.993 | D | 0.661 | prob.neutral | N | 0.483731686 | None | None | N |
| P/V | 0.259 | likely_benign | 0.2412 | benign | -0.843 | Destabilizing | 0.995 | D | 0.652 | prob.neutral | None | None | None | None | N |
| P/W | 0.7658 | likely_pathogenic | 0.7504 | pathogenic | -1.328 | Destabilizing | 1.0 | D | 0.635 | neutral | None | None | None | None | N |
| P/Y | 0.5544 | ambiguous | 0.5241 | ambiguous | -1.077 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | 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.