Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 947 | 3064;3065;3066 | chr2:178783722;178783721;178783720 | chr2:179648449;179648448;179648447 |
| N2AB | 947 | 3064;3065;3066 | chr2:178783722;178783721;178783720 | chr2:179648449;179648448;179648447 |
| N2A | 947 | 3064;3065;3066 | chr2:178783722;178783721;178783720 | chr2:179648449;179648448;179648447 |
| N2B | 901 | 2926;2927;2928 | chr2:178783722;178783721;178783720 | chr2:179648449;179648448;179648447 |
| Novex-1 | 901 | 2926;2927;2928 | chr2:178783722;178783721;178783720 | chr2:179648449;179648448;179648447 |
| Novex-2 | 901 | 2926;2927;2928 | chr2:178783722;178783721;178783720 | chr2:179648449;179648448;179648447 |
| Novex-3 | 947 | 3064;3065;3066 | chr2:178783722;178783721;178783720 | chr2:179648449;179648448;179648447 |
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/L | rs761200839  |
0.233 | 0.919 | N | 0.386 | 0.368 | None | gnomAD-2.1.1 | 4.38E-05 | None | None | None | None | N | None | 1.23031E-04 | 8.67E-05 | None | 0 | 1.08921E-04 | None | 3.27E-05 | None | 0 | 8.8E-06 | 3.26371E-04 |
| S/L | rs761200839 |
0.233 | 0.919 | N | 0.386 | 0.368 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 2.42E-05 | 2.62605E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/L | rs761200839 |
0.233 | 0.919 | N | 0.386 | 0.368 | None | gnomAD-4.0.0 | 1.98408E-05 | None | None | None | None | N | None | 4.01241E-05 | 1.0008E-04 | None | 0 | 8.92618E-05 | None | 0 | 0 | 1.0175E-05 | 3.29562E-05 | 6.40779E-05 |
| S/P | None | None | 0.966 | N | 0.373 | 0.546 | 0.344945010812 | gnomAD-4.0.0 | 1.59137E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85819E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0967 | likely_benign | 0.1078 | benign | -0.469 | Destabilizing | 0.022 | N | 0.132 | neutral | N | 0.502534838 | None | None | N |
| S/C | 0.2058 | likely_benign | 0.276 | benign | -0.318 | Destabilizing | 0.998 | D | 0.386 | neutral | None | None | None | None | N |
| S/D | 0.5827 | likely_pathogenic | 0.6906 | pathogenic | -0.079 | Destabilizing | 0.842 | D | 0.365 | neutral | None | None | None | None | N |
| S/E | 0.5849 | likely_pathogenic | 0.6799 | pathogenic | -0.123 | Destabilizing | 0.842 | D | 0.325 | neutral | None | None | None | None | N |
| S/F | 0.3365 | likely_benign | 0.4534 | ambiguous | -0.702 | Destabilizing | 0.904 | D | 0.443 | neutral | None | None | None | None | N |
| S/G | 0.1825 | likely_benign | 0.2231 | benign | -0.677 | Destabilizing | 0.525 | D | 0.357 | neutral | None | None | None | None | N |
| S/H | 0.488 | ambiguous | 0.5716 | pathogenic | -1.12 | Destabilizing | 0.998 | D | 0.387 | neutral | None | None | None | None | N |
| S/I | 0.365 | ambiguous | 0.4784 | ambiguous | -0.036 | Destabilizing | 0.949 | D | 0.419 | neutral | None | None | None | None | N |
| S/K | 0.7704 | likely_pathogenic | 0.8474 | pathogenic | -0.75 | Destabilizing | 0.842 | D | 0.331 | neutral | None | None | None | None | N |
| S/L | 0.1605 | likely_benign | 0.2068 | benign | -0.036 | Destabilizing | 0.919 | D | 0.386 | neutral | N | 0.500052215 | None | None | N |
| S/M | 0.325 | likely_benign | 0.386 | ambiguous | 0.152 | Stabilizing | 0.991 | D | 0.393 | neutral | None | None | None | None | N |
| S/N | 0.2808 | likely_benign | 0.3477 | ambiguous | -0.523 | Destabilizing | 0.842 | D | 0.383 | neutral | None | None | None | None | N |
| S/P | 0.8631 | likely_pathogenic | 0.9447 | pathogenic | -0.147 | Destabilizing | 0.966 | D | 0.373 | neutral | N | 0.513409637 | None | None | N |
| S/Q | 0.5863 | likely_pathogenic | 0.6558 | pathogenic | -0.701 | Destabilizing | 0.974 | D | 0.391 | neutral | None | None | None | None | N |
| S/R | 0.6731 | likely_pathogenic | 0.7816 | pathogenic | -0.545 | Destabilizing | 0.949 | D | 0.371 | neutral | None | None | None | None | N |
| S/T | 0.1213 | likely_benign | 0.1394 | benign | -0.567 | Destabilizing | 0.051 | N | 0.147 | neutral | N | 0.461941709 | None | None | N |
| S/V | 0.3186 | likely_benign | 0.3962 | ambiguous | -0.147 | Destabilizing | 0.728 | D | 0.391 | neutral | None | None | None | None | N |
| S/W | 0.4241 | ambiguous | 0.5891 | pathogenic | -0.713 | Destabilizing | 0.069 | N | 0.361 | neutral | N | 0.508939591 | None | None | N |
| S/Y | 0.2586 | likely_benign | 0.3602 | ambiguous | -0.467 | Destabilizing | 0.904 | D | 0.443 | neutral | 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.