Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30213 | 90862;90863;90864 | chr2:178552263;178552262;178552261 | chr2:179416990;179416989;179416988 |
| N2AB | 28572 | 85939;85940;85941 | chr2:178552263;178552262;178552261 | chr2:179416990;179416989;179416988 |
| N2A | 27645 | 83158;83159;83160 | chr2:178552263;178552262;178552261 | chr2:179416990;179416989;179416988 |
| N2B | 21148 | 63667;63668;63669 | chr2:178552263;178552262;178552261 | chr2:179416990;179416989;179416988 |
| Novex-1 | 21273 | 64042;64043;64044 | chr2:178552263;178552262;178552261 | chr2:179416990;179416989;179416988 |
| Novex-2 | 21340 | 64243;64244;64245 | chr2:178552263;178552262;178552261 | chr2:179416990;179416989;179416988 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs114026724  |
-1.54 | None | N | 0.14 | 0.084 | None | gnomAD-2.1.1 | 1.93234E-03 | None | None | None | None | I | None | 2.06731E-02 | 7.08255E-04 | None | 0 | 1.02543E-04 | None | 1.31044E-04 | None | 0 | 3.14E-05 | 7.03631E-04 |
| I/T | rs114026724 |
-1.54 | None | N | 0.14 | 0.084 | None | gnomAD-3.1.2 | 5.5565E-03 | None | None | None | None | I | None | 1.94564E-02 | 1.44187E-03 | 0 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 2.07297E-04 | 5.26316E-03 |
| I/T | rs114026724 |
-1.54 | None | N | 0.14 | 0.084 | None | 1000 genomes | 6.58946E-03 | None | None | None | None | I | None | 2.34E-02 | 2.9E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/T | rs114026724 |
-1.54 | None | N | 0.14 | 0.084 | None | gnomAD-4.0.0 | 1.03813E-03 | None | None | None | None | I | None | 1.8997E-02 | 9.50507E-04 | None | 3.37929E-05 | 6.68866E-05 | None | 0 | 3.3036E-04 | 7.2057E-05 | 9.88859E-05 | 1.48886E-03 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1405 | likely_benign | 0.1335 | benign | -1.037 | Destabilizing | 0.002 | N | 0.269 | neutral | None | None | None | None | I |
| I/C | 0.3875 | ambiguous | 0.3961 | ambiguous | -0.696 | Destabilizing | 0.245 | N | 0.369 | neutral | None | None | None | None | I |
| I/D | 0.3413 | ambiguous | 0.3051 | benign | -0.662 | Destabilizing | 0.004 | N | 0.339 | neutral | None | None | None | None | I |
| I/E | 0.2664 | likely_benign | 0.2408 | benign | -0.716 | Destabilizing | 0.004 | N | 0.338 | neutral | None | None | None | None | I |
| I/F | 0.1583 | likely_benign | 0.154 | benign | -0.797 | Destabilizing | 0.065 | N | 0.321 | neutral | N | 0.453045541 | None | None | I |
| I/G | 0.407 | ambiguous | 0.3784 | ambiguous | -1.271 | Destabilizing | 0.002 | N | 0.323 | neutral | None | None | None | None | I |
| I/H | 0.1722 | likely_benign | 0.1717 | benign | -0.464 | Destabilizing | 0.044 | N | 0.53 | neutral | None | None | None | None | I |
| I/K | 0.1162 | likely_benign | 0.0988 | benign | -0.742 | Destabilizing | None | N | 0.214 | neutral | None | None | None | None | I |
| I/L | 0.1072 | likely_benign | 0.1067 | benign | -0.511 | Destabilizing | 0.001 | N | 0.197 | neutral | N | 0.46082486 | None | None | I |
| I/M | 0.0791 | likely_benign | 0.0842 | benign | -0.488 | Destabilizing | 0.196 | N | 0.362 | neutral | N | 0.488608894 | None | None | I |
| I/N | 0.0807 | likely_benign | 0.0726 | benign | -0.545 | Destabilizing | None | N | 0.227 | neutral | N | 0.436257276 | None | None | I |
| I/P | 0.8722 | likely_pathogenic | 0.8319 | pathogenic | -0.653 | Destabilizing | 0.037 | N | 0.423 | neutral | None | None | None | None | I |
| I/Q | 0.1632 | likely_benign | 0.1567 | benign | -0.758 | Destabilizing | 0.018 | N | 0.423 | neutral | None | None | None | None | I |
| I/R | 0.1179 | likely_benign | 0.1033 | benign | -0.117 | Destabilizing | 0.004 | N | 0.356 | neutral | None | None | None | None | I |
| I/S | 0.1185 | likely_benign | 0.106 | benign | -1.016 | Destabilizing | 0.001 | N | 0.293 | neutral | N | 0.446087481 | None | None | I |
| I/T | 0.0849 | likely_benign | 0.0741 | benign | -0.959 | Destabilizing | None | N | 0.14 | neutral | N | 0.452725452 | None | None | I |
| I/V | 0.0707 | likely_benign | 0.0748 | benign | -0.653 | Destabilizing | 0.001 | N | 0.211 | neutral | N | 0.401680556 | None | None | I |
| I/W | 0.6813 | likely_pathogenic | 0.6798 | pathogenic | -0.834 | Destabilizing | 0.788 | D | 0.431 | neutral | None | None | None | None | I |
| I/Y | 0.267 | likely_benign | 0.2518 | benign | -0.611 | Destabilizing | 0.085 | N | 0.427 | 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.