Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24046 | 72361;72362;72363 | chr2:178573996;178573995;178573994 | chr2:179438723;179438722;179438721 |
| N2AB | 22405 | 67438;67439;67440 | chr2:178573996;178573995;178573994 | chr2:179438723;179438722;179438721 |
| N2A | 21478 | 64657;64658;64659 | chr2:178573996;178573995;178573994 | chr2:179438723;179438722;179438721 |
| N2B | 14981 | 45166;45167;45168 | chr2:178573996;178573995;178573994 | chr2:179438723;179438722;179438721 |
| Novex-1 | 15106 | 45541;45542;45543 | chr2:178573996;178573995;178573994 | chr2:179438723;179438722;179438721 |
| Novex-2 | 15173 | 45742;45743;45744 | chr2:178573996;178573995;178573994 | chr2:179438723;179438722;179438721 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/V | rs146767076  |
-0.15 | None | N | 0.11 | 0.07 | None | gnomAD-2.1.1 | 4.65023E-04 | None | None | None | None | N | None | 4.79854E-03 | 3.1165E-04 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 7.83E-06 | 1.40766E-04 |
| A/V | rs146767076 |
-0.15 | None | N | 0.11 | 0.07 | None | gnomAD-3.1.2 | 1.28881E-03 | None | None | None | None | N | None | 4.44166E-03 | 6.55566E-04 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 1.47E-05 | 0 | 0 |
| A/V | rs146767076 |
-0.15 | None | N | 0.11 | 0.07 | None | 1000 genomes | 1.39776E-03 | None | None | None | None | N | None | 5.3E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| A/V | rs146767076 |
-0.15 | None | N | 0.11 | 0.07 | None | gnomAD-4.0.0 | 2.36774E-04 | None | None | None | None | N | None | 4.50619E-03 | 4.16833E-04 | None | 0 | 0 | None | 0 | 1.65125E-04 | 2.54323E-06 | 2.19621E-05 | 2.08147E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.3723 | ambiguous | 0.3791 | ambiguous | -0.817 | Destabilizing | 0.667 | D | 0.395 | neutral | None | None | None | None | N |
| A/D | 0.2125 | likely_benign | 0.2377 | benign | -0.5 | Destabilizing | 0.22 | N | 0.365 | neutral | None | None | None | None | N |
| A/E | 0.2027 | likely_benign | 0.2216 | benign | -0.579 | Destabilizing | 0.175 | N | 0.353 | neutral | N | 0.412897627 | None | None | N |
| A/F | 0.2379 | likely_benign | 0.2878 | benign | -0.935 | Destabilizing | 0.22 | N | 0.363 | neutral | None | None | None | None | N |
| A/G | 0.1138 | likely_benign | 0.1164 | benign | -0.875 | Destabilizing | 0.175 | N | 0.269 | neutral | N | 0.50434635 | None | None | N |
| A/H | 0.3691 | ambiguous | 0.3906 | ambiguous | -0.874 | Destabilizing | 0.958 | D | 0.375 | neutral | None | None | None | None | N |
| A/I | 0.1287 | likely_benign | 0.1572 | benign | -0.335 | Destabilizing | 0.002 | N | 0.15 | neutral | None | None | None | None | N |
| A/K | 0.3545 | ambiguous | 0.386 | ambiguous | -0.86 | Destabilizing | 0.22 | N | 0.363 | neutral | None | None | None | None | N |
| A/L | 0.1103 | likely_benign | 0.1255 | benign | -0.335 | Destabilizing | None | N | 0.15 | neutral | None | None | None | None | N |
| A/M | 0.1366 | likely_benign | 0.1653 | benign | -0.312 | Destabilizing | 0.025 | N | 0.277 | neutral | None | None | None | None | N |
| A/N | 0.1475 | likely_benign | 0.1609 | benign | -0.529 | Destabilizing | 0.497 | N | 0.414 | neutral | None | None | None | None | N |
| A/P | 0.1074 | likely_benign | 0.1135 | benign | -0.41 | Destabilizing | 0.301 | N | 0.435 | neutral | N | 0.391714278 | None | None | N |
| A/Q | 0.2776 | likely_benign | 0.2887 | benign | -0.732 | Destabilizing | 0.667 | D | 0.401 | neutral | None | None | None | None | N |
| A/R | 0.3308 | likely_benign | 0.3507 | ambiguous | -0.463 | Destabilizing | 0.497 | N | 0.432 | neutral | None | None | None | None | N |
| A/S | 0.0756 | likely_benign | 0.0763 | benign | -0.913 | Destabilizing | 0.042 | N | 0.293 | neutral | N | 0.383150723 | None | None | N |
| A/T | 0.0675 | likely_benign | 0.0744 | benign | -0.891 | Destabilizing | None | N | 0.121 | neutral | N | 0.360871296 | None | None | N |
| A/V | 0.085 | likely_benign | 0.0975 | benign | -0.41 | Destabilizing | None | N | 0.11 | neutral | N | 0.410070752 | None | None | N |
| A/W | 0.6295 | likely_pathogenic | 0.6609 | pathogenic | -1.156 | Destabilizing | 0.958 | D | 0.41 | neutral | None | None | None | None | N |
| A/Y | 0.3394 | likely_benign | 0.3793 | ambiguous | -0.778 | Destabilizing | 0.667 | D | 0.395 | 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.