Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4016 | 12271;12272;12273 | chr2:178741187;178741186;178741185 | chr2:179605914;179605913;179605912 |
| N2AB | 3699 | 11320;11321;11322 | chr2:178741187;178741186;178741185 | chr2:179605914;179605913;179605912 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3653 | 11182;11183;11184 | chr2:178741187;178741186;178741185 | chr2:179605914;179605913;179605912 |
| Novex-1 | 3778 | 11557;11558;11559 | chr2:178741187;178741186;178741185 | chr2:179605914;179605913;179605912 |
| Novex-2 | 3845 | 11758;11759;11760 | chr2:178741187;178741186;178741185 | chr2:179605914;179605913;179605912 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs528996964  |
0.425 | None | N | 0.138 | 0.116 | None | gnomAD-2.1.1 | 4.29E-05 | None | None | None | None | I | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.61E-05 | 0 |
| M/I | rs528996964 |
0.425 | None | N | 0.138 | 0.116 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/I | rs528996964 |
0.425 | None | N | 0.138 | 0.116 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| M/I | rs528996964 |
0.425 | None | N | 0.138 | 0.116 | None | gnomAD-4.0.0 | 1.85941E-06 | None | None | None | None | I | None | 1.33262E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69514E-06 | 0 | 0 |
| M/T | rs760386971 |
0.646 | None | N | 0.167 | 0.095 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| M/T | rs760386971 |
0.646 | None | N | 0.167 | 0.095 | None | gnomAD-4.0.0 | 4.77699E-06 | None | None | None | None | I | None | 0 | 2.28666E-05 | None | 0 | 0 | None | 0 | 0 | 2.85791E-06 | 0 | 3.02444E-05 |
| M/V | rs908523887 |
0.352 | None | N | 0.137 | 0.082 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 0 | 0 |
| M/V | rs908523887 |
0.352 | None | N | 0.137 | 0.082 | None | gnomAD-4.0.0 | 6.36949E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 5.73099E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.1729 | likely_benign | 0.1904 | benign | -0.168 | Destabilizing | None | N | 0.17 | neutral | None | None | None | None | I |
| M/C | 0.5636 | ambiguous | 0.5651 | pathogenic | -0.366 | Destabilizing | 0.041 | N | 0.331 | neutral | None | None | None | None | I |
| M/D | 0.3759 | ambiguous | 0.4042 | ambiguous | 0.414 | Stabilizing | 0.002 | N | 0.333 | neutral | None | None | None | None | I |
| M/E | 0.1895 | likely_benign | 0.2113 | benign | 0.354 | Stabilizing | 0.001 | N | 0.269 | neutral | None | None | None | None | I |
| M/F | 0.2415 | likely_benign | 0.2422 | benign | -0.081 | Destabilizing | 0.004 | N | 0.256 | neutral | None | None | None | None | I |
| M/G | 0.3173 | likely_benign | 0.3418 | ambiguous | -0.279 | Destabilizing | 0.001 | N | 0.276 | neutral | None | None | None | None | I |
| M/H | 0.2918 | likely_benign | 0.3007 | benign | 0.416 | Stabilizing | 0.041 | N | 0.401 | neutral | None | None | None | None | I |
| M/I | 0.15 | likely_benign | 0.1663 | benign | 0.024 | Stabilizing | None | N | 0.138 | neutral | N | 0.430323848 | None | None | I |
| M/K | 0.1045 | likely_benign | 0.1117 | benign | 0.482 | Stabilizing | None | N | 0.172 | neutral | N | 0.426477469 | None | None | I |
| M/L | 0.0933 | likely_benign | 0.0996 | benign | 0.024 | Stabilizing | None | N | 0.138 | neutral | N | 0.431162133 | None | None | I |
| M/N | 0.2362 | likely_benign | 0.2627 | benign | 0.585 | Stabilizing | 0.004 | N | 0.328 | neutral | None | None | None | None | I |
| M/P | 0.3017 | likely_benign | 0.3023 | benign | -0.015 | Destabilizing | None | N | 0.193 | neutral | None | None | None | None | I |
| M/Q | 0.1511 | likely_benign | 0.1716 | benign | 0.442 | Stabilizing | None | N | 0.157 | neutral | None | None | None | None | I |
| M/R | 0.1026 | likely_benign | 0.1065 | benign | 0.907 | Stabilizing | None | N | 0.175 | neutral | N | 0.426233489 | None | None | I |
| M/S | 0.1882 | likely_benign | 0.2083 | benign | 0.178 | Stabilizing | None | N | 0.169 | neutral | None | None | None | None | I |
| M/T | 0.0911 | likely_benign | 0.0944 | benign | 0.212 | Stabilizing | None | N | 0.167 | neutral | N | 0.42288028 | None | None | I |
| M/V | 0.061 | likely_benign | 0.0624 | benign | -0.015 | Destabilizing | None | N | 0.137 | neutral | N | 0.435107728 | None | None | I |
| M/W | 0.4669 | ambiguous | 0.4603 | ambiguous | -0.109 | Destabilizing | 0.316 | N | 0.289 | neutral | None | None | None | None | I |
| M/Y | 0.3906 | ambiguous | 0.3867 | ambiguous | 0.096 | Stabilizing | 0.018 | N | 0.364 | neutral | 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.