Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5756 | 17491;17492;17493 | chr2:178731500;178731499;178731498 | chr2:179596227;179596226;179596225 |
| N2AB | 5439 | 16540;16541;16542 | chr2:178731500;178731499;178731498 | chr2:179596227;179596226;179596225 |
| N2A | 4512 | 13759;13760;13761 | chr2:178731500;178731499;178731498 | chr2:179596227;179596226;179596225 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs367634185  |
-0.321 | 1.0 | N | 0.617 | 0.492 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/C | rs367634185 |
-0.321 | 1.0 | N | 0.617 | 0.492 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/C | rs367634185 |
-0.321 | 1.0 | N | 0.617 | 0.492 | None | gnomAD-4.0.0 | 6.57263E-06 | None | None | None | None | I | None | 2.41255E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/F | rs367634185 |
None | 0.999 | D | 0.686 | 0.462 | 0.727048445308 | gnomAD-4.0.0 | 1.59185E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85887E-06 | 0 | 0 |
| S/P | rs2080496775 |
None | 0.999 | N | 0.603 | 0.501 | 0.399740851666 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/P | rs2080496775 |
None | 0.999 | N | 0.603 | 0.501 | 0.399740851666 | gnomAD-4.0.0 | 6.57333E-06 | None | None | None | None | I | None | 0 | 6.54879E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1614 | likely_benign | 0.1686 | benign | -0.133 | Destabilizing | 0.987 | D | 0.489 | neutral | N | 0.485199031 | None | None | I |
| S/C | 0.2932 | likely_benign | 0.2757 | benign | -0.361 | Destabilizing | 1.0 | D | 0.617 | neutral | N | 0.498836742 | None | None | I |
| S/D | 0.795 | likely_pathogenic | 0.78 | pathogenic | 0.165 | Stabilizing | 0.996 | D | 0.569 | neutral | None | None | None | None | I |
| S/E | 0.8943 | likely_pathogenic | 0.8862 | pathogenic | 0.079 | Stabilizing | 0.992 | D | 0.562 | neutral | None | None | None | None | I |
| S/F | 0.4174 | ambiguous | 0.4554 | ambiguous | -0.781 | Destabilizing | 0.999 | D | 0.686 | prob.neutral | D | 0.526421573 | None | None | I |
| S/G | 0.2552 | likely_benign | 0.2557 | benign | -0.227 | Destabilizing | 0.996 | D | 0.479 | neutral | None | None | None | None | I |
| S/H | 0.7185 | likely_pathogenic | 0.7091 | pathogenic | -0.553 | Destabilizing | 1.0 | D | 0.592 | neutral | None | None | None | None | I |
| S/I | 0.5286 | ambiguous | 0.5724 | pathogenic | -0.022 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | I |
| S/K | 0.9679 | likely_pathogenic | 0.9648 | pathogenic | -0.381 | Destabilizing | 0.983 | D | 0.514 | neutral | None | None | None | None | I |
| S/L | 0.2917 | likely_benign | 0.3181 | benign | -0.022 | Destabilizing | 0.996 | D | 0.611 | neutral | None | None | None | None | I |
| S/M | 0.4867 | ambiguous | 0.519 | ambiguous | -0.129 | Destabilizing | 1.0 | D | 0.596 | neutral | None | None | None | None | I |
| S/N | 0.4557 | ambiguous | 0.4636 | ambiguous | -0.147 | Destabilizing | 0.996 | D | 0.576 | neutral | None | None | None | None | I |
| S/P | 0.7537 | likely_pathogenic | 0.7211 | pathogenic | -0.031 | Destabilizing | 0.999 | D | 0.603 | neutral | N | 0.498836742 | None | None | I |
| S/Q | 0.8718 | likely_pathogenic | 0.8697 | pathogenic | -0.327 | Destabilizing | 0.999 | D | 0.583 | neutral | None | None | None | None | I |
| S/R | 0.9406 | likely_pathogenic | 0.9377 | pathogenic | -0.153 | Destabilizing | 0.784 | D | 0.399 | neutral | None | None | None | None | I |
| S/T | 0.1433 | likely_benign | 0.1457 | benign | -0.223 | Destabilizing | 0.994 | D | 0.514 | neutral | N | 0.516511224 | None | None | I |
| S/V | 0.4857 | ambiguous | 0.5194 | ambiguous | -0.031 | Destabilizing | 0.999 | D | 0.645 | neutral | None | None | None | None | I |
| S/W | 0.6308 | likely_pathogenic | 0.637 | pathogenic | -0.877 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| S/Y | 0.4193 | ambiguous | 0.4419 | ambiguous | -0.545 | Destabilizing | 0.999 | D | 0.69 | prob.neutral | D | 0.526421573 | 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.