Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30577 | 91954;91955;91956 | chr2:178550109;178550108;178550107 | chr2:179414836;179414835;179414834 |
| N2AB | 28936 | 87031;87032;87033 | chr2:178550109;178550108;178550107 | chr2:179414836;179414835;179414834 |
| N2A | 28009 | 84250;84251;84252 | chr2:178550109;178550108;178550107 | chr2:179414836;179414835;179414834 |
| N2B | 21512 | 64759;64760;64761 | chr2:178550109;178550108;178550107 | chr2:179414836;179414835;179414834 |
| Novex-1 | 21637 | 65134;65135;65136 | chr2:178550109;178550108;178550107 | chr2:179414836;179414835;179414834 |
| Novex-2 | 21704 | 65335;65336;65337 | chr2:178550109;178550108;178550107 | chr2:179414836;179414835;179414834 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs727505073  |
None | 0.653 | N | 0.411 | 0.097 | 0.136095386433 | 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 |
| D/E | rs727505073 |
None | 0.653 | N | 0.411 | 0.097 | 0.136095386433 | gnomAD-4.0.0 | 2.47883E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39048E-06 | 0 | 0 |
| D/N | rs781699152 |
0.593 | 0.806 | N | 0.377 | 0.262 | 0.215869574891 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.66E-05 | 0 |
| D/N | rs781699152 |
0.593 | 0.806 | N | 0.377 | 0.262 | 0.215869574891 | gnomAD-4.0.0 | 4.7894E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.6984E-06 | 3.4781E-05 | 1.65651E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2621 | likely_benign | 0.2328 | benign | -0.267 | Destabilizing | 0.139 | N | 0.498 | neutral | N | 0.462234022 | None | None | I |
| D/C | 0.7198 | likely_pathogenic | 0.6861 | pathogenic | 0.21 | Stabilizing | 0.995 | D | 0.553 | neutral | None | None | None | None | I |
| D/E | 0.2151 | likely_benign | 0.1795 | benign | -0.296 | Destabilizing | 0.653 | D | 0.411 | neutral | N | 0.457289562 | None | None | I |
| D/F | 0.7638 | likely_pathogenic | 0.7476 | pathogenic | -0.341 | Destabilizing | 0.944 | D | 0.565 | neutral | None | None | None | None | I |
| D/G | 0.2843 | likely_benign | 0.2563 | benign | -0.456 | Destabilizing | 0.002 | N | 0.317 | neutral | N | 0.470432218 | None | None | I |
| D/H | 0.3789 | ambiguous | 0.3417 | ambiguous | -0.339 | Destabilizing | 0.99 | D | 0.524 | neutral | N | 0.465141041 | None | None | I |
| D/I | 0.5965 | likely_pathogenic | 0.5461 | ambiguous | 0.179 | Stabilizing | 0.704 | D | 0.57 | neutral | None | None | None | None | I |
| D/K | 0.5737 | likely_pathogenic | 0.5161 | ambiguous | 0.43 | Stabilizing | 0.704 | D | 0.497 | neutral | None | None | None | None | I |
| D/L | 0.5874 | likely_pathogenic | 0.5528 | ambiguous | 0.179 | Stabilizing | 0.543 | D | 0.587 | neutral | None | None | None | None | I |
| D/M | 0.7165 | likely_pathogenic | 0.6887 | pathogenic | 0.42 | Stabilizing | 0.981 | D | 0.555 | neutral | None | None | None | None | I |
| D/N | 0.1235 | likely_benign | 0.1098 | benign | 0.172 | Stabilizing | 0.806 | D | 0.377 | neutral | N | 0.373692318 | None | None | I |
| D/P | 0.7955 | likely_pathogenic | 0.7335 | pathogenic | 0.053 | Stabilizing | 0.828 | D | 0.539 | neutral | None | None | None | None | I |
| D/Q | 0.4672 | ambiguous | 0.417 | ambiguous | 0.194 | Stabilizing | 0.828 | D | 0.43 | neutral | None | None | None | None | I |
| D/R | 0.582 | likely_pathogenic | 0.537 | ambiguous | 0.452 | Stabilizing | 0.704 | D | 0.564 | neutral | None | None | None | None | I |
| D/S | 0.1555 | likely_benign | 0.1384 | benign | 0.079 | Stabilizing | 0.037 | N | 0.245 | neutral | None | None | None | None | I |
| D/T | 0.2911 | likely_benign | 0.2563 | benign | 0.227 | Stabilizing | 0.004 | N | 0.329 | neutral | None | None | None | None | I |
| D/V | 0.3695 | ambiguous | 0.3347 | benign | 0.053 | Stabilizing | 0.473 | N | 0.589 | neutral | N | 0.444648339 | None | None | I |
| D/W | 0.9197 | likely_pathogenic | 0.9181 | pathogenic | -0.247 | Destabilizing | 0.995 | D | 0.558 | neutral | None | None | None | None | I |
| D/Y | 0.3656 | ambiguous | 0.3381 | benign | -0.109 | Destabilizing | 0.99 | D | 0.561 | neutral | N | 0.450806307 | 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.