Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5956 | 18091;18092;18093 | chr2:178730667;178730666;178730665 | chr2:179595394;179595393;179595392 |
| N2AB | 5639 | 17140;17141;17142 | chr2:178730667;178730666;178730665 | chr2:179595394;179595393;179595392 |
| N2A | 4712 | 14359;14360;14361 | chr2:178730667;178730666;178730665 | chr2:179595394;179595393;179595392 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs879248826  |
None | 0.051 | N | 0.178 | 0.072 | 0.130388298395 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.45E-05 | 0 | 0 | 0 | 0 |
| D/E | rs879248826 |
None | 0.051 | N | 0.178 | 0.072 | 0.130388298395 | gnomAD-4.0.0 | 1.36851E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79904E-06 | 0 | 0 |
| D/V | rs1322586586 |
0.135 | 0.966 | N | 0.44 | 0.341 | 0.474722520063 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/V | rs1322586586 |
0.135 | 0.966 | N | 0.44 | 0.341 | 0.474722520063 | gnomAD-4.0.0 | 1.5915E-06 | None | None | None | None | N | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1721 | likely_benign | 0.1813 | benign | -0.254 | Destabilizing | 0.669 | D | 0.353 | neutral | N | 0.490995838 | None | None | N |
| D/C | 0.5734 | likely_pathogenic | 0.5761 | pathogenic | -0.046 | Destabilizing | 0.998 | D | 0.487 | neutral | None | None | None | None | N |
| D/E | 0.1312 | likely_benign | 0.1313 | benign | -0.223 | Destabilizing | 0.051 | N | 0.178 | neutral | N | 0.479642694 | None | None | N |
| D/F | 0.5646 | likely_pathogenic | 0.564 | pathogenic | -0.178 | Destabilizing | 0.991 | D | 0.434 | neutral | None | None | None | None | N |
| D/G | 0.0782 | likely_benign | 0.087 | benign | -0.435 | Destabilizing | 0.005 | N | 0.215 | neutral | N | 0.344530833 | None | None | N |
| D/H | 0.2069 | likely_benign | 0.203 | benign | 0.107 | Stabilizing | 0.966 | D | 0.355 | neutral | N | 0.46141656 | None | None | N |
| D/I | 0.426 | ambiguous | 0.4442 | ambiguous | 0.172 | Stabilizing | 0.991 | D | 0.434 | neutral | None | None | None | None | N |
| D/K | 0.2318 | likely_benign | 0.2355 | benign | 0.287 | Stabilizing | 0.842 | D | 0.344 | neutral | None | None | None | None | N |
| D/L | 0.3876 | ambiguous | 0.3916 | ambiguous | 0.172 | Stabilizing | 0.974 | D | 0.44 | neutral | None | None | None | None | N |
| D/M | 0.5661 | likely_pathogenic | 0.5521 | ambiguous | 0.215 | Stabilizing | 0.998 | D | 0.437 | neutral | None | None | None | None | N |
| D/N | 0.0704 | likely_benign | 0.0724 | benign | 0.027 | Stabilizing | 0.051 | N | 0.233 | neutral | N | 0.440777662 | None | None | N |
| D/P | 0.8315 | likely_pathogenic | 0.8542 | pathogenic | 0.051 | Stabilizing | 0.991 | D | 0.377 | neutral | None | None | None | None | N |
| D/Q | 0.2174 | likely_benign | 0.2135 | benign | 0.059 | Stabilizing | 0.949 | D | 0.335 | neutral | None | None | None | None | N |
| D/R | 0.267 | likely_benign | 0.2617 | benign | 0.504 | Stabilizing | 0.949 | D | 0.417 | neutral | None | None | None | None | N |
| D/S | 0.0933 | likely_benign | 0.0982 | benign | -0.099 | Destabilizing | 0.842 | D | 0.329 | neutral | None | None | None | None | N |
| D/T | 0.221 | likely_benign | 0.2308 | benign | 0.045 | Stabilizing | 0.842 | D | 0.371 | neutral | None | None | None | None | N |
| D/V | 0.3027 | likely_benign | 0.3144 | benign | 0.051 | Stabilizing | 0.966 | D | 0.44 | neutral | N | 0.473444429 | None | None | N |
| D/W | 0.8711 | likely_pathogenic | 0.861 | pathogenic | -0.048 | Destabilizing | 0.998 | D | 0.558 | neutral | None | None | None | None | N |
| D/Y | 0.2453 | likely_benign | 0.2446 | benign | 0.059 | Stabilizing | 0.989 | D | 0.433 | neutral | N | 0.468417999 | 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.