Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6906 | 20941;20942;20943 | chr2:178725488;178725487;178725486 | chr2:179590215;179590214;179590213 |
| N2AB | 6589 | 19990;19991;19992 | chr2:178725488;178725487;178725486 | chr2:179590215;179590214;179590213 |
| N2A | 5662 | 17209;17210;17211 | chr2:178725488;178725487;178725486 | chr2:179590215;179590214;179590213 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1560728367  |
None | 0.425 | N | 0.198 | 0.134 | 0.58541340546 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/A | rs1560728367 |
None | 0.425 | N | 0.198 | 0.134 | 0.58541340546 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| V/E | None | None | 0.01 | N | 0.178 | 0.24 | 0.709453217969 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 0 |
| V/L | None | None | 0.053 | N | 0.205 | 0.14 | 0.442567846599 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.0862 | likely_benign | 0.0806 | benign | -0.539 | Destabilizing | 0.425 | N | 0.198 | neutral | N | 0.490748775 | None | None | I |
| V/C | 0.5897 | likely_pathogenic | 0.5217 | ambiguous | -0.687 | Destabilizing | 0.995 | D | 0.313 | neutral | None | None | None | None | I |
| V/D | 0.1377 | likely_benign | 0.1338 | benign | -0.181 | Destabilizing | 0.543 | D | 0.343 | neutral | None | None | None | None | I |
| V/E | 0.1211 | likely_benign | 0.1148 | benign | -0.27 | Destabilizing | 0.01 | N | 0.178 | neutral | N | 0.405705949 | None | None | I |
| V/F | 0.1036 | likely_benign | 0.0946 | benign | -0.602 | Destabilizing | 0.007 | N | 0.202 | neutral | None | None | None | None | I |
| V/G | 0.1193 | likely_benign | 0.1128 | benign | -0.697 | Destabilizing | 0.784 | D | 0.343 | neutral | N | 0.504544791 | None | None | I |
| V/H | 0.2574 | likely_benign | 0.2237 | benign | -0.165 | Destabilizing | 0.017 | N | 0.313 | neutral | None | None | None | None | I |
| V/I | 0.0762 | likely_benign | 0.071 | benign | -0.266 | Destabilizing | 0.329 | N | 0.223 | neutral | None | None | None | None | I |
| V/K | 0.1453 | likely_benign | 0.1335 | benign | -0.489 | Destabilizing | 0.704 | D | 0.34 | neutral | None | None | None | None | I |
| V/L | 0.1177 | likely_benign | 0.1055 | benign | -0.266 | Destabilizing | 0.053 | N | 0.205 | neutral | N | 0.480667854 | None | None | I |
| V/M | 0.1032 | likely_benign | 0.0915 | benign | -0.413 | Destabilizing | 0.065 | N | 0.134 | neutral | N | 0.518455451 | None | None | I |
| V/N | 0.133 | likely_benign | 0.1164 | benign | -0.299 | Destabilizing | 0.704 | D | 0.409 | neutral | None | None | None | None | I |
| V/P | 0.5436 | ambiguous | 0.5618 | ambiguous | -0.322 | Destabilizing | 0.981 | D | 0.399 | neutral | None | None | None | None | I |
| V/Q | 0.1387 | likely_benign | 0.1268 | benign | -0.496 | Destabilizing | 0.704 | D | 0.4 | neutral | None | None | None | None | I |
| V/R | 0.1203 | likely_benign | 0.1121 | benign | 0.013 | Stabilizing | 0.893 | D | 0.419 | neutral | None | None | None | None | I |
| V/S | 0.0902 | likely_benign | 0.0814 | benign | -0.7 | Destabilizing | 0.704 | D | 0.341 | neutral | None | None | None | None | I |
| V/T | 0.0885 | likely_benign | 0.0805 | benign | -0.682 | Destabilizing | 0.704 | D | 0.146 | neutral | None | None | None | None | I |
| V/W | 0.512 | ambiguous | 0.4762 | ambiguous | -0.692 | Destabilizing | 0.995 | D | 0.375 | neutral | None | None | None | None | I |
| V/Y | 0.3253 | likely_benign | 0.2873 | benign | -0.404 | Destabilizing | 0.543 | D | 0.329 | 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.