Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19405 | 58438;58439;58440 | chr2:178594180;178594179;178594178 | chr2:179458907;179458906;179458905 |
| N2AB | 17764 | 53515;53516;53517 | chr2:178594180;178594179;178594178 | chr2:179458907;179458906;179458905 |
| N2A | 16837 | 50734;50735;50736 | chr2:178594180;178594179;178594178 | chr2:179458907;179458906;179458905 |
| N2B | 10340 | 31243;31244;31245 | chr2:178594180;178594179;178594178 | chr2:179458907;179458906;179458905 |
| Novex-1 | 10465 | 31618;31619;31620 | chr2:178594180;178594179;178594178 | chr2:179458907;179458906;179458905 |
| Novex-2 | 10532 | 31819;31820;31821 | chr2:178594180;178594179;178594178 | chr2:179458907;179458906;179458905 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/D | None | None | 0.175 | N | 0.452 | 0.206 | 0.281780670237 | gnomAD-4.0.0 | 2.05319E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69878E-06 | 0 | 0 |
| A/T | None | None | 0.001 | N | 0.201 | 0.087 | 0.130388298395 | gnomAD-4.0.0 | 6.36894E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.14378E-05 | 0 | 0 |
| A/V | None | None | None | N | 0.182 | 0.071 | 0.15556083564 | gnomAD-4.0.0 | 6.84398E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99594E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.2707 | likely_benign | 0.2625 | benign | -0.705 | Destabilizing | 0.667 | D | 0.448 | neutral | None | None | None | None | I |
| A/D | 0.4035 | ambiguous | 0.3379 | benign | -0.717 | Destabilizing | 0.175 | N | 0.452 | neutral | N | 0.462230369 | None | None | I |
| A/E | 0.2916 | likely_benign | 0.2427 | benign | -0.718 | Destabilizing | 0.22 | N | 0.441 | neutral | None | None | None | None | I |
| A/F | 0.2208 | likely_benign | 0.2073 | benign | -0.688 | Destabilizing | 0.497 | N | 0.525 | neutral | None | None | None | None | I |
| A/G | 0.1557 | likely_benign | 0.1513 | benign | -0.892 | Destabilizing | None | N | 0.187 | neutral | N | 0.505770503 | None | None | I |
| A/H | 0.3225 | likely_benign | 0.3007 | benign | -0.894 | Destabilizing | 0.859 | D | 0.476 | neutral | None | None | None | None | I |
| A/I | 0.1559 | likely_benign | 0.1442 | benign | -0.065 | Destabilizing | 0.004 | N | 0.244 | neutral | None | None | None | None | I |
| A/K | 0.3773 | ambiguous | 0.3333 | benign | -0.893 | Destabilizing | 0.22 | N | 0.441 | neutral | None | None | None | None | I |
| A/L | 0.1236 | likely_benign | 0.12 | benign | -0.065 | Destabilizing | 0.025 | N | 0.315 | neutral | None | None | None | None | I |
| A/M | 0.1766 | likely_benign | 0.1641 | benign | -0.242 | Destabilizing | 0.025 | N | 0.282 | neutral | None | None | None | None | I |
| A/N | 0.2385 | likely_benign | 0.2157 | benign | -0.712 | Destabilizing | 0.22 | N | 0.457 | neutral | None | None | None | None | I |
| A/P | 0.5859 | likely_pathogenic | 0.566 | pathogenic | -0.212 | Destabilizing | 0.301 | N | 0.475 | neutral | N | 0.505770503 | None | None | I |
| A/Q | 0.2737 | likely_benign | 0.2531 | benign | -0.792 | Destabilizing | 0.667 | D | 0.513 | neutral | None | None | None | None | I |
| A/R | 0.298 | likely_benign | 0.2678 | benign | -0.619 | Destabilizing | 0.22 | N | 0.505 | neutral | None | None | None | None | I |
| A/S | 0.0866 | likely_benign | 0.0837 | benign | -1.073 | Destabilizing | 0.001 | N | 0.199 | neutral | N | 0.408126525 | None | None | I |
| A/T | 0.0722 | likely_benign | 0.0699 | benign | -0.961 | Destabilizing | 0.001 | N | 0.201 | neutral | N | 0.37312573 | None | None | I |
| A/V | 0.0957 | likely_benign | 0.0888 | benign | -0.212 | Destabilizing | None | N | 0.182 | neutral | N | 0.385190951 | None | None | I |
| A/W | 0.6424 | likely_pathogenic | 0.5954 | pathogenic | -1.042 | Destabilizing | 0.958 | D | 0.493 | neutral | None | None | None | None | I |
| A/Y | 0.3389 | likely_benign | 0.3133 | benign | -0.588 | Destabilizing | 0.667 | D | 0.491 | 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.