Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20713 | 62362;62363;62364 | chr2:178589588;178589587;178589586 | chr2:179454315;179454314;179454313 |
| N2AB | 19072 | 57439;57440;57441 | chr2:178589588;178589587;178589586 | chr2:179454315;179454314;179454313 |
| N2A | 18145 | 54658;54659;54660 | chr2:178589588;178589587;178589586 | chr2:179454315;179454314;179454313 |
| N2B | 11648 | 35167;35168;35169 | chr2:178589588;178589587;178589586 | chr2:179454315;179454314;179454313 |
| Novex-1 | 11773 | 35542;35543;35544 | chr2:178589588;178589587;178589586 | chr2:179454315;179454314;179454313 |
| Novex-2 | 11840 | 35743;35744;35745 | chr2:178589588;178589587;178589586 | chr2:179454315;179454314;179454313 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs1177521349  |
0.623 | 0.248 | N | 0.388 | 0.062 | 0.139678290688 | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| D/N | rs1177521349 |
0.623 | 0.248 | N | 0.388 | 0.062 | 0.139678290688 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 4.83E-05 | 1.31113E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/N | rs1177521349 |
0.623 | 0.248 | N | 0.388 | 0.062 | 0.139678290688 | gnomAD-4.0.0 | 1.4257E-05 | None | None | None | None | N | None | 4.0063E-05 | 5.00367E-05 | None | 0 | 0 | None | 0 | 0 | 1.27164E-05 | 1.09823E-05 | 1.60128E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.0664 | likely_benign | 0.1153 | benign | 0.093 | Stabilizing | None | N | 0.181 | neutral | N | 0.47374659 | None | None | N |
| D/C | 0.3249 | likely_benign | 0.6275 | pathogenic | -0.008 | Destabilizing | 0.676 | D | 0.349 | neutral | None | None | None | None | N |
| D/E | 0.0758 | likely_benign | 0.1248 | benign | -0.292 | Destabilizing | None | N | 0.119 | neutral | N | 0.414215497 | None | None | N |
| D/F | 0.3245 | likely_benign | 0.6006 | pathogenic | -0.076 | Destabilizing | 0.356 | N | 0.361 | neutral | None | None | None | None | N |
| D/G | 0.0856 | likely_benign | 0.1412 | benign | 0.006 | Stabilizing | 0.012 | N | 0.479 | neutral | N | 0.434801413 | None | None | N |
| D/H | 0.1514 | likely_benign | 0.3003 | benign | 0.478 | Stabilizing | 0.515 | D | 0.397 | neutral | N | 0.472761136 | None | None | N |
| D/I | 0.1437 | likely_benign | 0.2849 | benign | 0.249 | Stabilizing | 0.038 | N | 0.392 | neutral | None | None | None | None | N |
| D/K | 0.1229 | likely_benign | 0.1993 | benign | 0.515 | Stabilizing | 0.016 | N | 0.441 | neutral | None | None | None | None | N |
| D/L | 0.1502 | likely_benign | 0.2542 | benign | 0.249 | Stabilizing | 0.016 | N | 0.358 | neutral | None | None | None | None | N |
| D/M | 0.2249 | likely_benign | 0.4782 | ambiguous | 0.107 | Stabilizing | 0.356 | N | 0.354 | neutral | None | None | None | None | N |
| D/N | 0.0651 | likely_benign | 0.0994 | benign | 0.364 | Stabilizing | 0.248 | N | 0.388 | neutral | N | 0.443634326 | None | None | N |
| D/P | 0.1928 | likely_benign | 0.3508 | ambiguous | 0.215 | Stabilizing | None | N | 0.271 | neutral | None | None | None | None | N |
| D/Q | 0.1275 | likely_benign | 0.2395 | benign | 0.345 | Stabilizing | 0.038 | N | 0.378 | neutral | None | None | None | None | N |
| D/R | 0.1685 | likely_benign | 0.3117 | benign | 0.656 | Stabilizing | 0.072 | N | 0.391 | neutral | None | None | None | None | N |
| D/S | 0.0608 | likely_benign | 0.0851 | benign | 0.261 | Stabilizing | 0.016 | N | 0.334 | neutral | None | None | None | None | N |
| D/T | 0.0771 | likely_benign | 0.1457 | benign | 0.335 | Stabilizing | None | N | 0.189 | neutral | None | None | None | None | N |
| D/V | 0.0996 | likely_benign | 0.1606 | benign | 0.215 | Stabilizing | 0.012 | N | 0.361 | neutral | N | 0.46889813 | None | None | N |
| D/W | 0.6571 | likely_pathogenic | 0.8465 | pathogenic | -0.071 | Destabilizing | 0.864 | D | 0.335 | neutral | None | None | None | None | N |
| D/Y | 0.1776 | likely_benign | 0.3047 | benign | 0.143 | Stabilizing | 0.515 | D | 0.361 | neutral | N | 0.492852425 | 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.