Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35987 | 108184;108185;108186 | chr2:178527029;178527028;178527027 | chr2:179391756;179391755;179391754 |
| N2AB | 34346 | 103261;103262;103263 | chr2:178527029;178527028;178527027 | chr2:179391756;179391755;179391754 |
| N2A | 33419 | 100480;100481;100482 | chr2:178527029;178527028;178527027 | chr2:179391756;179391755;179391754 |
| N2B | 26922 | 80989;80990;80991 | chr2:178527029;178527028;178527027 | chr2:179391756;179391755;179391754 |
| Novex-1 | 27047 | 81364;81365;81366 | chr2:178527029;178527028;178527027 | chr2:179391756;179391755;179391754 |
| Novex-2 | 27114 | 81565;81566;81567 | chr2:178527029;178527028;178527027 | chr2:179391756;179391755;179391754 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/N | rs2154129767  |
None | None | N | 0.097 | 0.113 | 0.242825505644 | gnomAD-4.0.0 | 4.80136E-06 | None | None | None | -0.332(OBSL1) -0.321(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.25009E-06 | 0 | 0 |
| H/R | rs761091731 |
-0.778 | 0.003 | N | 0.213 | 0.073 | 0.235038932564 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | -1.72(OBSL1) -1.595(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| H/R | rs761091731 |
-0.778 | 0.003 | N | 0.213 | 0.073 | 0.235038932564 | gnomAD-4.0.0 | 1.36907E-06 | None | None | None | -1.72(OBSL1) -1.595(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99774E-07 | 0 | 1.65711E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.2389 | likely_benign | 0.3076 | benign | -0.385 | Destabilizing | None | N | 0.165 | neutral | None | None | None | -0.279(OBSL1) -0.303(OBSCN) | N |
| H/C | 0.1841 | likely_benign | 0.2211 | benign | 0.32 | Stabilizing | 0.316 | N | 0.383 | neutral | None | None | None | -0.368(OBSL1) -0.327(OBSCN) | N |
| H/D | 0.1411 | likely_benign | 0.1831 | benign | 0.024 | Stabilizing | 0.001 | N | 0.271 | neutral | N | 0.452057101 | None | -0.282(OBSL1) -0.309(OBSCN) | N |
| H/E | 0.2685 | likely_benign | 0.3638 | ambiguous | 0.085 | Stabilizing | 0.001 | N | 0.225 | neutral | None | None | None | -0.374(OBSL1) -0.4(OBSCN) | N |
| H/F | 0.3933 | ambiguous | 0.4702 | ambiguous | 0.469 | Stabilizing | 0.041 | N | 0.439 | neutral | None | None | None | 0.066(OBSL1) 0.023(OBSCN) | N |
| H/G | 0.317 | likely_benign | 0.3792 | ambiguous | -0.718 | Destabilizing | 0.001 | N | 0.205 | neutral | None | None | None | -0.184(OBSL1) -0.207(OBSCN) | N |
| H/I | 0.2677 | likely_benign | 0.3525 | ambiguous | 0.5 | Stabilizing | 0.004 | N | 0.426 | neutral | None | None | None | -0.593(OBSL1) -0.621(OBSCN) | N |
| H/K | 0.2154 | likely_benign | 0.2796 | benign | -0.261 | Destabilizing | 0.001 | N | 0.263 | neutral | None | None | None | -0.658(OBSL1) -0.587(OBSCN) | N |
| H/L | 0.1547 | likely_benign | 0.1838 | benign | 0.5 | Stabilizing | 0.001 | N | 0.327 | neutral | N | 0.479166344 | None | -0.593(OBSL1) -0.621(OBSCN) | N |
| H/M | 0.4389 | ambiguous | 0.5284 | ambiguous | 0.37 | Stabilizing | 0.132 | N | 0.402 | neutral | None | None | None | -0.615(OBSL1) -0.601(OBSCN) | N |
| H/N | 0.0445 | likely_benign | 0.0481 | benign | -0.172 | Destabilizing | None | N | 0.097 | neutral | N | 0.428006805 | None | -0.332(OBSL1) -0.321(OBSCN) | N |
| H/P | 0.5843 | likely_pathogenic | 0.5756 | pathogenic | 0.229 | Stabilizing | 0.013 | N | 0.347 | neutral | D | 0.525477424 | None | -0.484(OBSL1) -0.512(OBSCN) | N |
| H/Q | 0.1508 | likely_benign | 0.2044 | benign | -0.012 | Destabilizing | 0.007 | N | 0.225 | neutral | N | 0.453017106 | None | -0.27(OBSL1) -0.273(OBSCN) | N |
| H/R | 0.1107 | likely_benign | 0.1348 | benign | -0.741 | Destabilizing | 0.003 | N | 0.213 | neutral | N | 0.447747359 | None | -1.72(OBSL1) -1.595(OBSCN) | N |
| H/S | 0.1405 | likely_benign | 0.1768 | benign | -0.254 | Destabilizing | None | N | 0.119 | neutral | None | None | None | 0.123(OBSL1) 0.134(OBSCN) | N |
| H/T | 0.1667 | likely_benign | 0.2236 | benign | -0.091 | Destabilizing | None | N | 0.123 | neutral | None | None | None | 0.028(OBSL1) 0.041(OBSCN) | N |
| H/V | 0.249 | likely_benign | 0.3239 | benign | 0.229 | Stabilizing | 0.002 | N | 0.363 | neutral | None | None | None | -0.484(OBSL1) -0.512(OBSCN) | N |
| H/W | 0.5232 | ambiguous | 0.5777 | pathogenic | 0.656 | Stabilizing | 0.316 | N | 0.347 | neutral | None | None | None | 0.186(OBSL1) 0.168(OBSCN) | N |
| H/Y | 0.1178 | likely_benign | 0.1357 | benign | 0.877 | Stabilizing | 0.039 | N | 0.358 | neutral | N | 0.49584795 | None | 0.053(OBSL1) 0.028(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.