Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15123 | 45592;45593;45594 | chr2:178621351;178621350;178621349 | chr2:179486078;179486077;179486076 |
| N2AB | 13482 | 40669;40670;40671 | chr2:178621351;178621350;178621349 | chr2:179486078;179486077;179486076 |
| N2A | 12555 | 37888;37889;37890 | chr2:178621351;178621350;178621349 | chr2:179486078;179486077;179486076 |
| N2B | 6058 | 18397;18398;18399 | chr2:178621351;178621350;178621349 | chr2:179486078;179486077;179486076 |
| Novex-1 | 6183 | 18772;18773;18774 | chr2:178621351;178621350;178621349 | chr2:179486078;179486077;179486076 |
| Novex-2 | 6250 | 18973;18974;18975 | chr2:178621351;178621350;178621349 | chr2:179486078;179486077;179486076 |
| 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/M | rs1160173197  |
-0.221 | 0.782 | N | 0.521 | 0.109 | 0.53819168318 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.49E-05 | 0 |
| I/M | rs1160173197 |
-0.221 | 0.782 | N | 0.521 | 0.109 | 0.53819168318 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.95E-05 | 0 | 0 |
| I/M | rs1160173197 |
-0.221 | 0.782 | N | 0.521 | 0.109 | 0.53819168318 | gnomAD-4.0.0 | 1.05512E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.44206E-05 | 0 | 0 |
| I/S | None | None | 0.879 | N | 0.519 | 0.341 | 0.748536116192 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6583 | likely_pathogenic | 0.6329 | pathogenic | -0.694 | Destabilizing | 0.575 | D | 0.567 | neutral | None | None | None | None | N |
| I/C | 0.893 | likely_pathogenic | 0.8719 | pathogenic | -0.715 | Destabilizing | 0.991 | D | 0.56 | neutral | None | None | None | None | N |
| I/D | 0.8807 | likely_pathogenic | 0.8894 | pathogenic | 0.264 | Stabilizing | 0.967 | D | 0.603 | neutral | None | None | None | None | N |
| I/E | 0.7726 | likely_pathogenic | 0.778 | pathogenic | 0.201 | Stabilizing | 0.906 | D | 0.613 | neutral | None | None | None | None | N |
| I/F | 0.3001 | likely_benign | 0.3208 | benign | -0.537 | Destabilizing | 0.642 | D | 0.494 | neutral | D | 0.544135715 | None | None | N |
| I/G | 0.8966 | likely_pathogenic | 0.8878 | pathogenic | -0.888 | Destabilizing | 0.906 | D | 0.604 | neutral | None | None | None | None | N |
| I/H | 0.7203 | likely_pathogenic | 0.7142 | pathogenic | -0.12 | Destabilizing | 0.991 | D | 0.643 | neutral | None | None | None | None | N |
| I/K | 0.6476 | likely_pathogenic | 0.6746 | pathogenic | -0.275 | Destabilizing | 0.906 | D | 0.603 | neutral | None | None | None | None | N |
| I/L | 0.1223 | likely_benign | 0.12 | benign | -0.296 | Destabilizing | 0.001 | N | 0.116 | neutral | N | 0.447701129 | None | None | N |
| I/M | 0.2006 | likely_benign | 0.192 | benign | -0.355 | Destabilizing | 0.782 | D | 0.521 | neutral | N | 0.452273498 | None | None | N |
| I/N | 0.5115 | ambiguous | 0.5241 | ambiguous | -0.138 | Destabilizing | 0.957 | D | 0.617 | neutral | D | 0.544318023 | None | None | N |
| I/P | 0.95 | likely_pathogenic | 0.9488 | pathogenic | -0.395 | Destabilizing | 0.967 | D | 0.615 | neutral | None | None | None | None | N |
| I/Q | 0.6492 | likely_pathogenic | 0.637 | pathogenic | -0.311 | Destabilizing | 0.967 | D | 0.622 | neutral | None | None | None | None | N |
| I/R | 0.5672 | likely_pathogenic | 0.5954 | pathogenic | 0.204 | Stabilizing | 0.906 | D | 0.617 | neutral | None | None | None | None | N |
| I/S | 0.5636 | ambiguous | 0.5551 | ambiguous | -0.717 | Destabilizing | 0.879 | D | 0.519 | neutral | N | 0.473748286 | None | None | N |
| I/T | 0.4085 | ambiguous | 0.4338 | ambiguous | -0.665 | Destabilizing | 0.505 | D | 0.518 | neutral | N | 0.448340014 | None | None | N |
| I/V | 0.1125 | likely_benign | 0.117 | benign | -0.395 | Destabilizing | 0.013 | N | 0.129 | neutral | N | 0.446968239 | None | None | N |
| I/W | 0.9061 | likely_pathogenic | 0.9108 | pathogenic | -0.538 | Destabilizing | 0.991 | D | 0.713 | prob.delet. | None | None | None | None | N |
| I/Y | 0.7341 | likely_pathogenic | 0.7363 | pathogenic | -0.287 | Destabilizing | 0.906 | D | 0.555 | 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.