Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28478 | 85657;85658;85659 | chr2:178560700;178560699;178560698 | chr2:179425427;179425426;179425425 |
| N2AB | 26837 | 80734;80735;80736 | chr2:178560700;178560699;178560698 | chr2:179425427;179425426;179425425 |
| N2A | 25910 | 77953;77954;77955 | chr2:178560700;178560699;178560698 | chr2:179425427;179425426;179425425 |
| N2B | 19413 | 58462;58463;58464 | chr2:178560700;178560699;178560698 | chr2:179425427;179425426;179425425 |
| Novex-1 | 19538 | 58837;58838;58839 | chr2:178560700;178560699;178560698 | chr2:179425427;179425426;179425425 |
| Novex-2 | 19605 | 59038;59039;59040 | chr2:178560700;178560699;178560698 | chr2:179425427;179425426;179425425 |
| 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/N | rs375744985  |
-0.407 | None | N | 0.078 | 0.114 | None | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| D/N | rs375744985 |
-0.407 | None | N | 0.078 | 0.114 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 1.20616E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs375744985 |
-0.407 | None | N | 0.078 | 0.114 | None | gnomAD-4.0.0 | 7.43695E-06 | None | None | None | None | N | None | 1.46823E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60123E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.4282 | ambiguous | 0.4167 | ambiguous | -0.135 | Destabilizing | 0.052 | N | 0.525 | neutral | N | 0.500793346 | None | None | N |
| D/C | 0.8258 | likely_pathogenic | 0.8243 | pathogenic | 0.228 | Stabilizing | 0.935 | D | 0.565 | neutral | None | None | None | None | N |
| D/E | 0.5455 | ambiguous | 0.5296 | ambiguous | -0.515 | Destabilizing | 0.027 | N | 0.343 | neutral | N | 0.512616951 | None | None | N |
| D/F | 0.8633 | likely_pathogenic | 0.8346 | pathogenic | -0.333 | Destabilizing | 0.38 | N | 0.592 | neutral | None | None | None | None | N |
| D/G | 0.4651 | ambiguous | 0.4199 | ambiguous | -0.377 | Destabilizing | 0.027 | N | 0.442 | neutral | D | 0.526508151 | None | None | N |
| D/H | 0.6027 | likely_pathogenic | 0.5847 | pathogenic | -0.663 | Destabilizing | 0.317 | N | 0.493 | neutral | N | 0.514391377 | None | None | N |
| D/I | 0.5905 | likely_pathogenic | 0.6183 | pathogenic | 0.457 | Stabilizing | 0.081 | N | 0.547 | neutral | None | None | None | None | N |
| D/K | 0.7085 | likely_pathogenic | 0.7082 | pathogenic | 0.108 | Stabilizing | 0.081 | N | 0.452 | neutral | None | None | None | None | N |
| D/L | 0.7124 | likely_pathogenic | 0.6907 | pathogenic | 0.457 | Stabilizing | 0.001 | N | 0.283 | neutral | None | None | None | None | N |
| D/M | 0.8448 | likely_pathogenic | 0.8303 | pathogenic | 0.822 | Stabilizing | 0.38 | N | 0.571 | neutral | None | None | None | None | N |
| D/N | 0.1182 | likely_benign | 0.1174 | benign | -0.069 | Destabilizing | None | N | 0.078 | neutral | N | 0.500415903 | None | None | N |
| D/P | 0.8775 | likely_pathogenic | 0.8683 | pathogenic | 0.285 | Stabilizing | 0.555 | D | 0.467 | neutral | None | None | None | None | N |
| D/Q | 0.7445 | likely_pathogenic | 0.7246 | pathogenic | -0.015 | Destabilizing | 0.38 | N | 0.415 | neutral | None | None | None | None | N |
| D/R | 0.7416 | likely_pathogenic | 0.7352 | pathogenic | 0.055 | Stabilizing | 0.149 | N | 0.517 | neutral | None | None | None | None | N |
| D/S | 0.2517 | likely_benign | 0.2508 | benign | -0.204 | Destabilizing | 0.035 | N | 0.356 | neutral | None | None | None | None | N |
| D/T | 0.3876 | ambiguous | 0.3635 | ambiguous | -0.023 | Destabilizing | 0.081 | N | 0.433 | neutral | None | None | None | None | N |
| D/V | 0.4477 | ambiguous | 0.4642 | ambiguous | 0.285 | Stabilizing | 0.062 | N | 0.539 | neutral | D | 0.531988653 | None | None | N |
| D/W | 0.9574 | likely_pathogenic | 0.9543 | pathogenic | -0.345 | Destabilizing | 0.935 | D | 0.641 | neutral | None | None | None | None | N |
| D/Y | 0.3593 | ambiguous | 0.3611 | ambiguous | -0.138 | Destabilizing | 0.741 | D | 0.59 | neutral | D | 0.544612406 | 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.