Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27752 | 83479;83480;83481 | chr2:178562878;178562877;178562876 | chr2:179427605;179427604;179427603 |
| N2AB | 26111 | 78556;78557;78558 | chr2:178562878;178562877;178562876 | chr2:179427605;179427604;179427603 |
| N2A | 25184 | 75775;75776;75777 | chr2:178562878;178562877;178562876 | chr2:179427605;179427604;179427603 |
| N2B | 18687 | 56284;56285;56286 | chr2:178562878;178562877;178562876 | chr2:179427605;179427604;179427603 |
| Novex-1 | 18812 | 56659;56660;56661 | chr2:178562878;178562877;178562876 | chr2:179427605;179427604;179427603 |
| Novex-2 | 18879 | 56860;56861;56862 | chr2:178562878;178562877;178562876 | chr2:179427605;179427604;179427603 |
| 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 | None | None | 0.992 | N | 0.57 | 0.492 | 0.553591132476 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| S/G | None | None | 0.698 | N | 0.471 | 0.338 | 0.289474373501 | gnomAD-4.0.0 | 6.00161E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.56251E-06 | 0 | 0 |
| S/R | rs1704199409  |
None | 0.97 | D | 0.534 | 0.519 | 0.477762074677 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/R | rs1704199409 |
None | 0.97 | D | 0.534 | 0.519 | 0.477762074677 | gnomAD-4.0.0 | 6.57324E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47042E-05 | 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 | 0.0754 | likely_benign | 0.0769 | benign | -0.241 | Destabilizing | 0.019 | N | 0.323 | neutral | None | None | None | None | I |
| S/C | 0.0755 | likely_benign | 0.073 | benign | -0.379 | Destabilizing | 0.992 | D | 0.57 | neutral | N | 0.497026316 | None | None | I |
| S/D | 0.7143 | likely_pathogenic | 0.7059 | pathogenic | -0.201 | Destabilizing | 0.978 | D | 0.447 | neutral | None | None | None | None | I |
| S/E | 0.7733 | likely_pathogenic | 0.7619 | pathogenic | -0.312 | Destabilizing | 0.86 | D | 0.449 | neutral | None | None | None | None | I |
| S/F | 0.2745 | likely_benign | 0.263 | benign | -1.015 | Destabilizing | 0.978 | D | 0.663 | neutral | None | None | None | None | I |
| S/G | 0.0964 | likely_benign | 0.0988 | benign | -0.246 | Destabilizing | 0.698 | D | 0.471 | neutral | N | 0.501581766 | None | None | I |
| S/H | 0.449 | ambiguous | 0.4299 | ambiguous | -0.559 | Destabilizing | 0.998 | D | 0.571 | neutral | None | None | None | None | I |
| S/I | 0.1948 | likely_benign | 0.1762 | benign | -0.346 | Destabilizing | 0.125 | N | 0.515 | neutral | N | 0.507257023 | None | None | I |
| S/K | 0.84 | likely_pathogenic | 0.8228 | pathogenic | -0.406 | Destabilizing | 0.86 | D | 0.446 | neutral | None | None | None | None | I |
| S/L | 0.1429 | likely_benign | 0.134 | benign | -0.346 | Destabilizing | 0.754 | D | 0.574 | neutral | None | None | None | None | I |
| S/M | 0.2546 | likely_benign | 0.2368 | benign | -0.219 | Destabilizing | 0.994 | D | 0.549 | neutral | None | None | None | None | I |
| S/N | 0.244 | likely_benign | 0.2211 | benign | -0.148 | Destabilizing | 0.97 | D | 0.479 | neutral | N | 0.491999887 | None | None | I |
| S/P | 0.8474 | likely_pathogenic | 0.8855 | pathogenic | -0.292 | Destabilizing | 0.978 | D | 0.531 | neutral | None | None | None | None | I |
| S/Q | 0.6375 | likely_pathogenic | 0.6212 | pathogenic | -0.381 | Destabilizing | 0.978 | D | 0.481 | neutral | None | None | None | None | I |
| S/R | 0.7434 | likely_pathogenic | 0.7222 | pathogenic | -0.176 | Destabilizing | 0.97 | D | 0.534 | neutral | D | 0.525979898 | None | None | I |
| S/T | 0.1161 | likely_benign | 0.1171 | benign | -0.274 | Destabilizing | 0.822 | D | 0.497 | neutral | N | 0.491097606 | None | None | I |
| S/V | 0.1993 | likely_benign | 0.1868 | benign | -0.292 | Destabilizing | 0.754 | D | 0.567 | neutral | None | None | None | None | I |
| S/W | 0.4657 | ambiguous | 0.4784 | ambiguous | -1.104 | Destabilizing | 0.998 | D | 0.729 | prob.delet. | None | None | None | None | I |
| S/Y | 0.2795 | likely_benign | 0.2639 | benign | -0.8 | Destabilizing | 0.993 | D | 0.672 | 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.