Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26195 | 78808;78809;78810 | chr2:178567549;178567548;178567547 | chr2:179432276;179432275;179432274 |
| N2AB | 24554 | 73885;73886;73887 | chr2:178567549;178567548;178567547 | chr2:179432276;179432275;179432274 |
| N2A | 23627 | 71104;71105;71106 | chr2:178567549;178567548;178567547 | chr2:179432276;179432275;179432274 |
| N2B | 17130 | 51613;51614;51615 | chr2:178567549;178567548;178567547 | chr2:179432276;179432275;179432274 |
| Novex-1 | 17255 | 51988;51989;51990 | chr2:178567549;178567548;178567547 | chr2:179432276;179432275;179432274 |
| Novex-2 | 17322 | 52189;52190;52191 | chr2:178567549;178567548;178567547 | chr2:179432276;179432275;179432274 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/V | rs369118365  |
-0.595 | 0.01 | N | 0.058 | 0.195 | None | gnomAD-2.1.1 | 2.53E-05 | None | None | None | None | N | None | 4.14E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.95E-05 | 1.42776E-04 |
| M/V | rs369118365 |
-0.595 | 0.01 | N | 0.058 | 0.195 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| M/V | rs369118365 |
-0.595 | 0.01 | N | 0.058 | 0.195 | None | gnomAD-4.0.0 | 1.49076E-05 | None | None | None | None | N | None | 1.33701E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.95254E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.7126 | likely_pathogenic | 0.6487 | pathogenic | -2.384 | Highly Destabilizing | 0.55 | D | 0.189 | neutral | None | None | None | None | N |
| M/C | 0.8563 | likely_pathogenic | 0.8417 | pathogenic | -2.065 | Highly Destabilizing | 0.993 | D | 0.316 | neutral | None | None | None | None | N |
| M/D | 0.9876 | likely_pathogenic | 0.9821 | pathogenic | -1.54 | Destabilizing | 0.932 | D | 0.377 | neutral | None | None | None | None | N |
| M/E | 0.9465 | likely_pathogenic | 0.9289 | pathogenic | -1.324 | Destabilizing | 0.932 | D | 0.314 | neutral | None | None | None | None | N |
| M/F | 0.5438 | ambiguous | 0.5185 | ambiguous | -0.837 | Destabilizing | 0.932 | D | 0.201 | neutral | None | None | None | None | N |
| M/G | 0.9023 | likely_pathogenic | 0.8714 | pathogenic | -2.881 | Highly Destabilizing | 0.932 | D | 0.31 | neutral | None | None | None | None | N |
| M/H | 0.9579 | likely_pathogenic | 0.939 | pathogenic | -2.238 | Highly Destabilizing | 0.993 | D | 0.359 | neutral | None | None | None | None | N |
| M/I | 0.6159 | likely_pathogenic | 0.5475 | ambiguous | -0.966 | Destabilizing | 0.028 | N | 0.079 | neutral | N | 0.40483637 | None | None | N |
| M/K | 0.8233 | likely_pathogenic | 0.7665 | pathogenic | -1.3 | Destabilizing | 0.912 | D | 0.289 | neutral | N | 0.474898547 | None | None | N |
| M/L | 0.1582 | likely_benign | 0.1492 | benign | -0.966 | Destabilizing | 0.166 | N | 0.134 | neutral | N | 0.371971803 | None | None | N |
| M/N | 0.9477 | likely_pathogenic | 0.9223 | pathogenic | -1.586 | Destabilizing | 0.932 | D | 0.37 | neutral | None | None | None | None | N |
| M/P | 0.9584 | likely_pathogenic | 0.9433 | pathogenic | -1.418 | Destabilizing | 0.977 | D | 0.359 | neutral | None | None | None | None | N |
| M/Q | 0.8168 | likely_pathogenic | 0.7646 | pathogenic | -1.312 | Destabilizing | 0.977 | D | 0.249 | neutral | None | None | None | None | N |
| M/R | 0.8051 | likely_pathogenic | 0.7452 | pathogenic | -1.29 | Destabilizing | 0.912 | D | 0.357 | neutral | N | 0.47312412 | None | None | N |
| M/S | 0.8558 | likely_pathogenic | 0.8035 | pathogenic | -2.261 | Highly Destabilizing | 0.584 | D | 0.286 | neutral | None | None | None | None | N |
| M/T | 0.5949 | likely_pathogenic | 0.4999 | ambiguous | -1.902 | Destabilizing | 0.01 | N | 0.095 | neutral | N | 0.482219718 | None | None | N |
| M/V | 0.1379 | likely_benign | 0.1164 | benign | -1.418 | Destabilizing | 0.01 | N | 0.058 | neutral | N | 0.444258763 | None | None | N |
| M/W | 0.9241 | likely_pathogenic | 0.9037 | pathogenic | -1.025 | Destabilizing | 0.998 | D | 0.315 | neutral | None | None | None | None | N |
| M/Y | 0.9208 | likely_pathogenic | 0.8961 | pathogenic | -1.054 | Destabilizing | 0.993 | D | 0.396 | 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.