Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14960 | 45103;45104;45105 | chr2:178622705;178622704;178622703 | chr2:179487432;179487431;179487430 |
| N2AB | 13319 | 40180;40181;40182 | chr2:178622705;178622704;178622703 | chr2:179487432;179487431;179487430 |
| N2A | 12392 | 37399;37400;37401 | chr2:178622705;178622704;178622703 | chr2:179487432;179487431;179487430 |
| N2B | 5895 | 17908;17909;17910 | chr2:178622705;178622704;178622703 | chr2:179487432;179487431;179487430 |
| Novex-1 | 6020 | 18283;18284;18285 | chr2:178622705;178622704;178622703 | chr2:179487432;179487431;179487430 |
| Novex-2 | 6087 | 18484;18485;18486 | chr2:178622705;178622704;178622703 | chr2:179487432;179487431;179487430 |
| 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/P | rs764153170  |
None | 0.996 | D | 0.545 | 0.279 | 0.297718772494 | gnomAD-3.1.2 | 6.6E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/P | rs764153170 |
None | 0.996 | D | 0.545 | 0.279 | 0.297718772494 | gnomAD-4.0.0 | 6.59544E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47384E-05 | 0 | 0 |
| R/Q | rs764153170 |
-0.265 | 0.958 | N | 0.54 | 0.168 | None | gnomAD-2.1.1 | 2.07E-05 | None | None | None | None | N | None | 0 | 1.18455E-04 | None | 0 | 0 | None | 0 | None | 0 | 9.13E-06 | 0 |
| R/Q | rs764153170 |
-0.265 | 0.958 | N | 0.54 | 0.168 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 6.58E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs764153170 |
-0.265 | 0.958 | N | 0.54 | 0.168 | None | gnomAD-4.0.0 | 1.18234E-05 | None | None | None | None | N | None | 0 | 8.41978E-05 | None | 0 | 0 | None | 0 | 0 | 1.01974E-05 | 2.22856E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5732 | likely_pathogenic | 0.5286 | ambiguous | -0.347 | Destabilizing | 0.688 | D | 0.535 | neutral | None | None | None | None | N |
| R/C | 0.3192 | likely_benign | 0.297 | benign | -0.529 | Destabilizing | 0.998 | D | 0.529 | neutral | None | None | None | None | N |
| R/D | 0.8735 | likely_pathogenic | 0.8546 | pathogenic | 0.009 | Stabilizing | 0.728 | D | 0.542 | neutral | None | None | None | None | N |
| R/E | 0.5139 | ambiguous | 0.49 | ambiguous | 0.139 | Stabilizing | 0.067 | N | 0.261 | neutral | None | None | None | None | N |
| R/F | 0.7165 | likely_pathogenic | 0.6964 | pathogenic | -0.22 | Destabilizing | 0.949 | D | 0.55 | neutral | None | None | None | None | N |
| R/G | 0.5384 | ambiguous | 0.4774 | ambiguous | -0.638 | Destabilizing | 0.954 | D | 0.54 | neutral | N | 0.484542731 | None | None | N |
| R/H | 0.1476 | likely_benign | 0.1412 | benign | -0.994 | Destabilizing | 0.991 | D | 0.561 | neutral | None | None | None | None | N |
| R/I | 0.3201 | likely_benign | 0.3185 | benign | 0.42 | Stabilizing | 0.016 | N | 0.439 | neutral | None | None | None | None | N |
| R/K | 0.1316 | likely_benign | 0.1263 | benign | -0.369 | Destabilizing | 0.029 | N | 0.259 | neutral | None | None | None | None | N |
| R/L | 0.3575 | ambiguous | 0.3458 | ambiguous | 0.42 | Stabilizing | 0.679 | D | 0.519 | neutral | N | 0.447346609 | None | None | N |
| R/M | 0.4003 | ambiguous | 0.3926 | ambiguous | -0.164 | Destabilizing | 0.949 | D | 0.557 | neutral | None | None | None | None | N |
| R/N | 0.7441 | likely_pathogenic | 0.7214 | pathogenic | -0.169 | Destabilizing | 0.915 | D | 0.549 | neutral | None | None | None | None | N |
| R/P | 0.9479 | likely_pathogenic | 0.9232 | pathogenic | 0.187 | Stabilizing | 0.996 | D | 0.545 | neutral | D | 0.549274554 | None | None | N |
| R/Q | 0.1459 | likely_benign | 0.1403 | benign | -0.201 | Destabilizing | 0.958 | D | 0.54 | neutral | N | 0.45020853 | None | None | N |
| R/S | 0.599 | likely_pathogenic | 0.5593 | ambiguous | -0.726 | Destabilizing | 0.842 | D | 0.571 | neutral | None | None | None | None | N |
| R/T | 0.2848 | likely_benign | 0.2608 | benign | -0.414 | Destabilizing | 0.842 | D | 0.551 | neutral | None | None | None | None | N |
| R/V | 0.379 | ambiguous | 0.3732 | ambiguous | 0.187 | Stabilizing | 0.525 | D | 0.529 | neutral | None | None | None | None | N |
| R/W | 0.3282 | likely_benign | 0.2884 | benign | -0.057 | Destabilizing | 0.998 | D | 0.552 | neutral | None | None | None | None | N |
| R/Y | 0.5677 | likely_pathogenic | 0.5514 | ambiguous | 0.28 | Stabilizing | 0.991 | D | 0.539 | 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.