Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28779 | 86560;86561;86562 | chr2:178559797;178559796;178559795 | chr2:179424524;179424523;179424522 |
| N2AB | 27138 | 81637;81638;81639 | chr2:178559797;178559796;178559795 | chr2:179424524;179424523;179424522 |
| N2A | 26211 | 78856;78857;78858 | chr2:178559797;178559796;178559795 | chr2:179424524;179424523;179424522 |
| N2B | 19714 | 59365;59366;59367 | chr2:178559797;178559796;178559795 | chr2:179424524;179424523;179424522 |
| Novex-1 | 19839 | 59740;59741;59742 | chr2:178559797;178559796;178559795 | chr2:179424524;179424523;179424522 |
| Novex-2 | 19906 | 59941;59942;59943 | chr2:178559797;178559796;178559795 | chr2:179424524;179424523;179424522 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs763175453  |
0.023 | 0.998 | N | 0.492 | 0.306 | 0.21737058555 | gnomAD-2.1.1 | 3.28E-05 | None | None | None | None | I | None | 1.29316E-04 | 2.92E-05 | None | 0 | 0 | None | 3.35E-05 | None | 0 | 2.7E-05 | 1.69033E-04 |
| R/Q | rs763175453 |
0.023 | 0.998 | N | 0.492 | 0.306 | 0.21737058555 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/Q | rs763175453 |
0.023 | 0.998 | N | 0.492 | 0.306 | 0.21737058555 | gnomAD-4.0.0 | 2.98549E-05 | None | None | None | None | I | None | 4.00877E-05 | 1.67499E-05 | None | 0 | 0 | None | 0 | 0 | 2.80159E-05 | 1.10627E-04 | 1.60643E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.4479 | ambiguous | 0.429 | ambiguous | 0.03 | Stabilizing | 0.97 | D | 0.488 | neutral | None | None | None | None | I |
| R/C | 0.159 | likely_benign | 0.1571 | benign | -0.243 | Destabilizing | 1.0 | D | 0.607 | neutral | None | None | None | None | I |
| R/D | 0.8193 | likely_pathogenic | 0.8025 | pathogenic | -0.284 | Destabilizing | 0.996 | D | 0.497 | neutral | None | None | None | None | I |
| R/E | 0.4779 | ambiguous | 0.4526 | ambiguous | -0.241 | Destabilizing | 0.97 | D | 0.484 | neutral | None | None | None | None | I |
| R/F | 0.563 | ambiguous | 0.5196 | ambiguous | -0.279 | Destabilizing | 0.999 | D | 0.577 | neutral | None | None | None | None | I |
| R/G | 0.3631 | ambiguous | 0.3652 | ambiguous | -0.115 | Destabilizing | 0.992 | D | 0.457 | neutral | N | 0.488999336 | None | None | I |
| R/H | 0.0906 | likely_benign | 0.0863 | benign | -0.612 | Destabilizing | 0.999 | D | 0.524 | neutral | None | None | None | None | I |
| R/I | 0.3017 | likely_benign | 0.2766 | benign | 0.369 | Stabilizing | 0.999 | D | 0.579 | neutral | None | None | None | None | I |
| R/K | 0.0923 | likely_benign | 0.0934 | benign | -0.161 | Destabilizing | 0.155 | N | 0.251 | neutral | None | None | None | None | I |
| R/L | 0.2965 | likely_benign | 0.274 | benign | 0.369 | Stabilizing | 0.992 | D | 0.457 | neutral | N | 0.500947126 | None | None | I |
| R/M | 0.3252 | likely_benign | 0.322 | benign | -0.066 | Destabilizing | 1.0 | D | 0.531 | neutral | None | None | None | None | I |
| R/N | 0.6463 | likely_pathogenic | 0.6239 | pathogenic | -0.055 | Destabilizing | 0.996 | D | 0.474 | neutral | None | None | None | None | I |
| R/P | 0.9427 | likely_pathogenic | 0.9348 | pathogenic | 0.274 | Stabilizing | 0.999 | D | 0.561 | neutral | N | 0.493467917 | None | None | I |
| R/Q | 0.1054 | likely_benign | 0.1053 | benign | -0.101 | Destabilizing | 0.998 | D | 0.492 | neutral | N | 0.452403817 | None | None | I |
| R/S | 0.4769 | ambiguous | 0.4557 | ambiguous | -0.253 | Destabilizing | 0.97 | D | 0.499 | neutral | None | None | None | None | I |
| R/T | 0.2377 | likely_benign | 0.227 | benign | -0.101 | Destabilizing | 0.985 | D | 0.473 | neutral | None | None | None | None | I |
| R/V | 0.379 | ambiguous | 0.3474 | ambiguous | 0.274 | Stabilizing | 0.996 | D | 0.565 | neutral | None | None | None | None | I |
| R/W | 0.2032 | likely_benign | 0.1855 | benign | -0.446 | Destabilizing | 1.0 | D | 0.625 | neutral | None | None | None | None | I |
| R/Y | 0.4258 | ambiguous | 0.3797 | ambiguous | -0.038 | Destabilizing | 0.999 | D | 0.561 | 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.