Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21612 | 65059;65060;65061 | chr2:178584807;178584806;178584805 | chr2:179449534;179449533;179449532 |
| N2AB | 19971 | 60136;60137;60138 | chr2:178584807;178584806;178584805 | chr2:179449534;179449533;179449532 |
| N2A | 19044 | 57355;57356;57357 | chr2:178584807;178584806;178584805 | chr2:179449534;179449533;179449532 |
| N2B | 12547 | 37864;37865;37866 | chr2:178584807;178584806;178584805 | chr2:179449534;179449533;179449532 |
| Novex-1 | 12672 | 38239;38240;38241 | chr2:178584807;178584806;178584805 | chr2:179449534;179449533;179449532 |
| Novex-2 | 12739 | 38440;38441;38442 | chr2:178584807;178584806;178584805 | chr2:179449534;179449533;179449532 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/G | rs535324559  |
-0.32 | 0.454 | N | 0.353 | 0.227 | 0.275641507738 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| A/G | rs535324559 |
-0.32 | 0.454 | N | 0.353 | 0.227 | 0.275641507738 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.94401E-04 | None | 0 | 0 | 0 | 0 | 0 |
| A/G | rs535324559 |
-0.32 | 0.454 | N | 0.353 | 0.227 | 0.275641507738 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| A/G | rs535324559 |
-0.32 | 0.454 | N | 0.353 | 0.227 | 0.275641507738 | gnomAD-4.0.0 | 6.57445E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.94856E-04 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs535324559 |
0.047 | 0.051 | N | 0.243 | 0.162 | 0.322510055762 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/V | rs535324559 |
0.047 | 0.051 | N | 0.243 | 0.162 | 0.322510055762 | gnomAD-4.0.0 | 1.5919E-06 | None | None | None | None | I | None | 0 | 2.28686E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6006 | likely_pathogenic | 0.6226 | pathogenic | -0.841 | Destabilizing | 0.998 | D | 0.391 | neutral | None | None | None | None | I |
| A/D | 0.7512 | likely_pathogenic | 0.8273 | pathogenic | -0.496 | Destabilizing | 0.801 | D | 0.395 | neutral | N | 0.452680671 | None | None | I |
| A/E | 0.7053 | likely_pathogenic | 0.7746 | pathogenic | -0.62 | Destabilizing | 0.842 | D | 0.367 | neutral | None | None | None | None | I |
| A/F | 0.6456 | likely_pathogenic | 0.6634 | pathogenic | -0.938 | Destabilizing | 0.974 | D | 0.399 | neutral | None | None | None | None | I |
| A/G | 0.1732 | likely_benign | 0.2181 | benign | -0.62 | Destabilizing | 0.454 | N | 0.353 | neutral | N | 0.465764612 | None | None | I |
| A/H | 0.7493 | likely_pathogenic | 0.7821 | pathogenic | -0.678 | Destabilizing | 0.998 | D | 0.371 | neutral | None | None | None | None | I |
| A/I | 0.5168 | ambiguous | 0.5735 | pathogenic | -0.368 | Destabilizing | 0.728 | D | 0.366 | neutral | None | None | None | None | I |
| A/K | 0.864 | likely_pathogenic | 0.8995 | pathogenic | -0.809 | Destabilizing | 0.842 | D | 0.371 | neutral | None | None | None | None | I |
| A/L | 0.333 | likely_benign | 0.3735 | ambiguous | -0.368 | Destabilizing | 0.728 | D | 0.347 | neutral | None | None | None | None | I |
| A/M | 0.4161 | ambiguous | 0.4621 | ambiguous | -0.356 | Destabilizing | 0.974 | D | 0.353 | neutral | None | None | None | None | I |
| A/N | 0.442 | ambiguous | 0.495 | ambiguous | -0.498 | Destabilizing | 0.949 | D | 0.399 | neutral | None | None | None | None | I |
| A/P | 0.29 | likely_benign | 0.3596 | ambiguous | -0.374 | Destabilizing | 0.966 | D | 0.373 | neutral | N | 0.488833472 | None | None | I |
| A/Q | 0.5962 | likely_pathogenic | 0.6342 | pathogenic | -0.752 | Destabilizing | 0.974 | D | 0.382 | neutral | None | None | None | None | I |
| A/R | 0.8218 | likely_pathogenic | 0.8545 | pathogenic | -0.379 | Destabilizing | 0.949 | D | 0.385 | neutral | None | None | None | None | I |
| A/S | 0.1004 | likely_benign | 0.1144 | benign | -0.779 | Destabilizing | 0.022 | N | 0.109 | neutral | N | 0.382820728 | None | None | I |
| A/T | 0.1243 | likely_benign | 0.1593 | benign | -0.814 | Destabilizing | 0.051 | N | 0.233 | neutral | N | 0.424051275 | None | None | I |
| A/V | 0.2605 | likely_benign | 0.3219 | benign | -0.374 | Destabilizing | 0.051 | N | 0.243 | neutral | N | 0.490115978 | None | None | I |
| A/W | 0.9172 | likely_pathogenic | 0.9242 | pathogenic | -1.114 | Destabilizing | 0.998 | D | 0.552 | neutral | None | None | None | None | I |
| A/Y | 0.755 | likely_pathogenic | 0.7749 | pathogenic | -0.75 | Destabilizing | 0.991 | D | 0.387 | 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.