Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21201 | 63826;63827;63828 | chr2:178587708;178587707;178587706 | chr2:179452435;179452434;179452433 |
| N2AB | 19560 | 58903;58904;58905 | chr2:178587708;178587707;178587706 | chr2:179452435;179452434;179452433 |
| N2A | 18633 | 56122;56123;56124 | chr2:178587708;178587707;178587706 | chr2:179452435;179452434;179452433 |
| N2B | 12136 | 36631;36632;36633 | chr2:178587708;178587707;178587706 | chr2:179452435;179452434;179452433 |
| Novex-1 | 12261 | 37006;37007;37008 | chr2:178587708;178587707;178587706 | chr2:179452435;179452434;179452433 |
| Novex-2 | 12328 | 37207;37208;37209 | chr2:178587708;178587707;178587706 | chr2:179452435;179452434;179452433 |
| 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/L | None | None | 1.0 | N | 0.638 | 0.502 | 0.747437394213 | gnomAD-4.0.0 | 6.84595E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65777E-05 |
| R/Q | rs763273464  |
0.018 | 1.0 | N | 0.719 | 0.438 | 0.437420747294 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | I | None | 0 | 8.72E-05 | None | 0 | 0 | None | 0 | None | 9.31E-05 | 8.92E-06 | 0 |
| R/Q | rs763273464 |
0.018 | 1.0 | N | 0.719 | 0.438 | 0.437420747294 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs763273464 |
0.018 | 1.0 | N | 0.719 | 0.438 | 0.437420747294 | gnomAD-4.0.0 | 1.17811E-05 | None | None | None | None | I | None | 2.67173E-05 | 5.00617E-05 | None | 0 | 2.24014E-05 | None | 3.12656E-05 | 0 | 8.47906E-06 | 1.09876E-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 | 0.9737 | likely_pathogenic | 0.9694 | pathogenic | 0.12 | Stabilizing | 0.999 | D | 0.649 | neutral | None | None | None | None | I |
| R/C | 0.6096 | likely_pathogenic | 0.5806 | pathogenic | -0.084 | Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | I |
| R/D | 0.9904 | likely_pathogenic | 0.9894 | pathogenic | -0.248 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| R/E | 0.9286 | likely_pathogenic | 0.9194 | pathogenic | -0.199 | Destabilizing | 0.999 | D | 0.706 | prob.neutral | None | None | None | None | I |
| R/F | 0.9357 | likely_pathogenic | 0.9281 | pathogenic | -0.146 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| R/G | 0.9589 | likely_pathogenic | 0.9525 | pathogenic | -0.039 | Destabilizing | 1.0 | D | 0.638 | neutral | D | 0.527434702 | None | None | I |
| R/H | 0.3311 | likely_benign | 0.301 | benign | -0.563 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | I |
| R/I | 0.8203 | likely_pathogenic | 0.7739 | pathogenic | 0.496 | Stabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| R/K | 0.3704 | ambiguous | 0.3178 | benign | -0.021 | Destabilizing | 0.998 | D | 0.512 | neutral | None | None | None | None | I |
| R/L | 0.8406 | likely_pathogenic | 0.8161 | pathogenic | 0.496 | Stabilizing | 1.0 | D | 0.638 | neutral | N | 0.492694222 | None | None | I |
| R/M | 0.8998 | likely_pathogenic | 0.8758 | pathogenic | 0.024 | Stabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| R/N | 0.9602 | likely_pathogenic | 0.9532 | pathogenic | 0.125 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| R/P | 0.9953 | likely_pathogenic | 0.9951 | pathogenic | 0.389 | Stabilizing | 1.0 | D | 0.705 | prob.neutral | D | 0.539044497 | None | None | I |
| R/Q | 0.4215 | ambiguous | 0.3721 | ambiguous | 0.074 | Stabilizing | 1.0 | D | 0.719 | prob.delet. | N | 0.490946249 | None | None | I |
| R/S | 0.9678 | likely_pathogenic | 0.9624 | pathogenic | -0.062 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
| R/T | 0.9352 | likely_pathogenic | 0.9116 | pathogenic | 0.098 | Stabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | I |
| R/V | 0.8922 | likely_pathogenic | 0.8711 | pathogenic | 0.389 | Stabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | I |
| R/W | 0.6059 | likely_pathogenic | 0.5815 | pathogenic | -0.31 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | I |
| R/Y | 0.8176 | likely_pathogenic | 0.7988 | pathogenic | 0.098 | Stabilizing | 1.0 | D | 0.737 | prob.delet. | 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.