Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6822 | 20689;20690;20691 | chr2:178725858;178725857;178725856 | chr2:179590585;179590584;179590583 |
| N2AB | 6505 | 19738;19739;19740 | chr2:178725858;178725857;178725856 | chr2:179590585;179590584;179590583 |
| N2A | 5578 | 16957;16958;16959 | chr2:178725858;178725857;178725856 | chr2:179590585;179590584;179590583 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/H | None | None | 0.002 | D | 0.213 | 0.276 | 0.186928172975 | gnomAD-4.0.0 | 6.84645E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16023E-05 | 0 |
| N/K | None | None | 0.004 | N | 0.084 | 0.162 | 0.162503812791 | gnomAD-4.0.0 | 3.18487E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.72069E-06 | 0 | 0 |
| N/S | rs371518764  |
-0.485 | 0.001 | N | 0.093 | 0.171 | None | gnomAD-2.1.1 | 3.57E-05 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 0 | 1.02512E-04 | None | 0 | None | 0 | 4.69E-05 | 0 |
| N/S | rs371518764 |
-0.485 | 0.001 | N | 0.093 | 0.171 | None | gnomAD-3.1.2 | 7.23E-05 | None | None | None | None | N | None | 4.82E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.1763E-04 | 0 | 0 |
| N/S | rs371518764 |
-0.485 | 0.001 | N | 0.093 | 0.171 | None | gnomAD-4.0.0 | 6.63262E-05 | None | None | None | None | N | None | 2.67051E-05 | 1.66822E-05 | None | 0 | 4.45772E-05 | None | 0 | 0 | 8.05415E-05 | 0 | 1.12133E-04 |
| N/T | rs371518764 |
-0.311 | 0.017 | D | 0.205 | 0.19 | 0.186928172975 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| N/T | rs371518764 |
-0.311 | 0.017 | D | 0.205 | 0.19 | 0.186928172975 | gnomAD-4.0.0 | 6.8443E-07 | None | None | None | None | N | None | 0 | 2.23824E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.1742 | likely_benign | 0.181 | benign | -0.584 | Destabilizing | None | N | 0.14 | neutral | None | None | None | None | N |
| N/C | 0.2707 | likely_benign | 0.2844 | benign | 0.271 | Stabilizing | 0.954 | D | 0.35 | neutral | None | None | None | None | N |
| N/D | 0.1453 | likely_benign | 0.1606 | benign | -0.35 | Destabilizing | 0.022 | N | 0.213 | neutral | D | 0.533875982 | None | None | N |
| N/E | 0.408 | ambiguous | 0.4345 | ambiguous | -0.332 | Destabilizing | 0.091 | N | 0.227 | neutral | None | None | None | None | N |
| N/F | 0.5044 | ambiguous | 0.498 | ambiguous | -0.634 | Destabilizing | 0.866 | D | 0.379 | neutral | None | None | None | None | N |
| N/G | 0.165 | likely_benign | 0.1645 | benign | -0.848 | Destabilizing | None | N | 0.058 | neutral | None | None | None | None | N |
| N/H | 0.0887 | likely_benign | 0.092 | benign | -0.803 | Destabilizing | 0.002 | N | 0.213 | neutral | D | 0.539605585 | None | None | N |
| N/I | 0.3639 | ambiguous | 0.3526 | ambiguous | 0.049 | Stabilizing | 0.646 | D | 0.415 | neutral | D | 0.613080338 | None | None | N |
| N/K | 0.2802 | likely_benign | 0.291 | benign | -0.162 | Destabilizing | 0.004 | N | 0.084 | neutral | N | 0.50324643 | None | None | N |
| N/L | 0.2627 | likely_benign | 0.2498 | benign | 0.049 | Stabilizing | 0.254 | N | 0.408 | neutral | None | None | None | None | N |
| N/M | 0.3295 | likely_benign | 0.3116 | benign | 0.594 | Stabilizing | 0.88 | D | 0.351 | neutral | None | None | None | None | N |
| N/P | 0.6843 | likely_pathogenic | 0.6948 | pathogenic | -0.133 | Destabilizing | 0.129 | N | 0.407 | neutral | None | None | None | None | N |
| N/Q | 0.2733 | likely_benign | 0.2763 | benign | -0.721 | Destabilizing | 0.254 | N | 0.259 | neutral | None | None | None | None | N |
| N/R | 0.3128 | likely_benign | 0.3284 | benign | -0.105 | Destabilizing | 0.313 | N | 0.193 | neutral | None | None | None | None | N |
| N/S | 0.0699 | likely_benign | 0.0743 | benign | -0.53 | Destabilizing | 0.001 | N | 0.093 | neutral | N | 0.487911618 | None | None | N |
| N/T | 0.134 | likely_benign | 0.1338 | benign | -0.347 | Destabilizing | 0.017 | N | 0.205 | neutral | D | 0.564233669 | None | None | N |
| N/V | 0.3453 | ambiguous | 0.3309 | benign | -0.133 | Destabilizing | 0.028 | N | 0.397 | neutral | None | None | None | None | N |
| N/W | 0.7287 | likely_pathogenic | 0.7422 | pathogenic | -0.482 | Destabilizing | 0.987 | D | 0.369 | neutral | None | None | None | None | N |
| N/Y | 0.1714 | likely_benign | 0.1774 | benign | -0.271 | Destabilizing | 0.546 | D | 0.394 | neutral | D | 0.587340422 | 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.