Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35925 | 107998;107999;108000 | chr2:178527215;178527214;178527213 | chr2:179391942;179391941;179391940 |
| N2AB | 34284 | 103075;103076;103077 | chr2:178527215;178527214;178527213 | chr2:179391942;179391941;179391940 |
| N2A | 33357 | 100294;100295;100296 | chr2:178527215;178527214;178527213 | chr2:179391942;179391941;179391940 |
| N2B | 26860 | 80803;80804;80805 | chr2:178527215;178527214;178527213 | chr2:179391942;179391941;179391940 |
| Novex-1 | 26985 | 81178;81179;81180 | chr2:178527215;178527214;178527213 | chr2:179391942;179391941;179391940 |
| Novex-2 | 27052 | 81379;81380;81381 | chr2:178527215;178527214;178527213 | chr2:179391942;179391941;179391940 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs781497669  |
-0.691 | None | N | 0.125 | 0.078 | 0.126345400529 | gnomAD-2.1.1 | 2.41E-05 | None | None | None | 0.418(OBSL1) -0.173(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.43E-05 | 1.65618E-04 |
| T/A | rs781497669 |
-0.691 | None | N | 0.125 | 0.078 | 0.126345400529 | gnomAD-4.0.0 | 1.64201E-05 | None | None | None | 0.418(OBSL1) -0.173(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.06865E-05 | 0 | 1.65645E-05 |
| T/I | rs755111765 |
-0.07 | None | N | 0.197 | 0.187 | 0.280181792013 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | 0.224(OBSL1) -0.099(OBSCN) | N | None | 0 | 0 | None | 0 | 1.6715E-04 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs755111765 |
-0.07 | None | N | 0.197 | 0.187 | 0.280181792013 | gnomAD-4.0.0 | 4.77315E-06 | None | None | None | 0.224(OBSL1) -0.099(OBSCN) | N | None | 0 | 0 | None | 0 | 8.31901E-05 | None | 0 | 0 | 0 | 0 | 0 |
| T/S | None | None | 0.042 | N | 0.28 | 0.042 | 0.137902524267 | gnomAD-4.0.0 | 1.59105E-06 | None | None | None | -0.255(OBSL1) -0.352(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02371E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0674 | likely_benign | 0.0691 | benign | -0.578 | Destabilizing | None | N | 0.125 | neutral | N | 0.435954285 | None | 0.418(OBSL1) -0.173(OBSCN) | N |
| T/C | 0.4942 | ambiguous | 0.4792 | ambiguous | -0.33 | Destabilizing | 0.667 | D | 0.474 | neutral | None | None | None | -0.728(OBSL1) 0.338(OBSCN) | N |
| T/D | 0.3872 | ambiguous | 0.3548 | ambiguous | 0.137 | Stabilizing | 0.124 | N | 0.457 | neutral | None | None | None | -0.524(OBSL1) -0.111(OBSCN) | N |
| T/E | 0.2509 | likely_benign | 0.2368 | benign | 0.091 | Stabilizing | 0.002 | N | 0.194 | neutral | None | None | None | -0.642(OBSL1) -0.129(OBSCN) | N |
| T/F | 0.2099 | likely_benign | 0.2117 | benign | -0.867 | Destabilizing | 0.497 | N | 0.498 | neutral | None | None | None | 0.209(OBSL1) -0.034(OBSCN) | N |
| T/G | 0.3281 | likely_benign | 0.3192 | benign | -0.769 | Destabilizing | 0.055 | N | 0.516 | neutral | None | None | None | 0.45(OBSL1) -0.2(OBSCN) | N |
| T/H | 0.2607 | likely_benign | 0.2415 | benign | -1.083 | Destabilizing | 0.859 | D | 0.49 | neutral | None | None | None | 0.182(OBSL1) 0.396(OBSCN) | N |
| T/I | 0.0869 | likely_benign | 0.0983 | benign | -0.178 | Destabilizing | None | N | 0.197 | neutral | N | 0.496869458 | None | 0.224(OBSL1) -0.099(OBSCN) | N |
| T/K | 0.1454 | likely_benign | 0.1295 | benign | -0.58 | Destabilizing | 0.22 | N | 0.457 | neutral | None | None | None | -1.051(OBSL1) -0.009(OBSCN) | N |
| T/L | 0.0775 | likely_benign | 0.0799 | benign | -0.178 | Destabilizing | 0.009 | N | 0.327 | neutral | None | None | None | 0.224(OBSL1) -0.099(OBSCN) | N |
| T/M | 0.0817 | likely_benign | 0.0874 | benign | None | Stabilizing | 0.497 | N | 0.469 | neutral | None | None | None | 0.191(OBSL1) 0.563(OBSCN) | N |
| T/N | 0.1324 | likely_benign | 0.1272 | benign | -0.361 | Destabilizing | 0.301 | N | 0.361 | neutral | D | 0.526978934 | None | -0.253(OBSL1) -0.399(OBSCN) | N |
| T/P | 0.1023 | likely_benign | 0.0986 | benign | -0.281 | Destabilizing | 0.301 | N | 0.509 | neutral | N | 0.438821232 | None | 0.304(OBSL1) -0.121(OBSCN) | N |
| T/Q | 0.1934 | likely_benign | 0.1826 | benign | -0.543 | Destabilizing | 0.22 | N | 0.487 | neutral | None | None | None | -0.331(OBSL1) -0.206(OBSCN) | N |
| T/R | 0.1217 | likely_benign | 0.1117 | benign | -0.348 | Destabilizing | 0.22 | N | 0.503 | neutral | None | None | None | -0.963(OBSL1) 0.01(OBSCN) | N |
| T/S | 0.1184 | likely_benign | 0.1173 | benign | -0.606 | Destabilizing | 0.042 | N | 0.28 | neutral | N | 0.487305825 | None | -0.255(OBSL1) -0.352(OBSCN) | N |
| T/V | 0.0848 | likely_benign | 0.0929 | benign | -0.281 | Destabilizing | None | N | 0.129 | neutral | None | None | None | 0.304(OBSL1) -0.121(OBSCN) | N |
| T/W | 0.626 | likely_pathogenic | 0.5909 | pathogenic | -0.843 | Destabilizing | 0.958 | D | 0.495 | neutral | None | None | None | -0.194(OBSL1) 0.052(OBSCN) | N |
| T/Y | 0.2974 | likely_benign | 0.2729 | benign | -0.594 | Destabilizing | 0.667 | D | 0.496 | neutral | None | None | None | 0.283(OBSL1) 0.129(OBSCN) | 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.