Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21235 | 63928;63929;63930 | chr2:178587606;178587605;178587604 | chr2:179452333;179452332;179452331 |
| N2AB | 19594 | 59005;59006;59007 | chr2:178587606;178587605;178587604 | chr2:179452333;179452332;179452331 |
| N2A | 18667 | 56224;56225;56226 | chr2:178587606;178587605;178587604 | chr2:179452333;179452332;179452331 |
| N2B | 12170 | 36733;36734;36735 | chr2:178587606;178587605;178587604 | chr2:179452333;179452332;179452331 |
| Novex-1 | 12295 | 37108;37109;37110 | chr2:178587606;178587605;178587604 | chr2:179452333;179452332;179452331 |
| Novex-2 | 12362 | 37309;37310;37311 | chr2:178587606;178587605;178587604 | chr2:179452333;179452332;179452331 |
| 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/D | rs786205305  |
-0.074 | None | N | 0.13 | 0.075 | 0.158396225186 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| N/D | rs786205305 |
-0.074 | None | N | 0.13 | 0.075 | 0.158396225186 | gnomAD-4.0.0 | 1.59381E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43361E-05 | 0 |
| N/S | rs751607765 |
-0.097 | 0.042 | N | 0.356 | 0.159 | 0.15556083564 | gnomAD-2.1.1 | 2.15E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.30933E-04 | None | 0 | 1.57E-05 | 0 |
| N/S | rs751607765 |
-0.097 | 0.042 | N | 0.356 | 0.159 | 0.15556083564 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 6.20604E-04 | 0 |
| N/S | rs751607765 |
-0.097 | 0.042 | N | 0.356 | 0.159 | 0.15556083564 | gnomAD-4.0.0 | 2.10844E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.24185E-05 | None | 0 | 1.64853E-04 | 4.23955E-06 | 2.85576E-04 | 1.60246E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.1733 | likely_benign | 0.1875 | benign | -0.384 | Destabilizing | 0.104 | N | 0.372 | neutral | None | None | None | None | N |
| N/C | 0.2648 | likely_benign | 0.2885 | benign | 0.4 | Stabilizing | 0.958 | D | 0.429 | neutral | None | None | None | None | N |
| N/D | 0.1152 | likely_benign | 0.1062 | benign | -0.003 | Destabilizing | None | N | 0.13 | neutral | N | 0.463443877 | None | None | N |
| N/E | 0.262 | likely_benign | 0.2725 | benign | -0.035 | Destabilizing | 0.001 | N | 0.115 | neutral | None | None | None | None | N |
| N/F | 0.5264 | ambiguous | 0.5577 | ambiguous | -0.76 | Destabilizing | 0.859 | D | 0.441 | neutral | None | None | None | None | N |
| N/G | 0.2202 | likely_benign | 0.2364 | benign | -0.564 | Destabilizing | 0.104 | N | 0.321 | neutral | None | None | None | None | N |
| N/H | 0.1072 | likely_benign | 0.1128 | benign | -0.668 | Destabilizing | 0.822 | D | 0.375 | neutral | N | 0.472104983 | None | None | N |
| N/I | 0.2834 | likely_benign | 0.296 | benign | 0.005 | Stabilizing | 0.602 | D | 0.457 | neutral | N | 0.498464898 | None | None | N |
| N/K | 0.2951 | likely_benign | 0.3079 | benign | 0.128 | Stabilizing | 0.081 | N | 0.273 | neutral | N | 0.483261789 | None | None | N |
| N/L | 0.2566 | likely_benign | 0.2685 | benign | 0.005 | Stabilizing | 0.364 | N | 0.459 | neutral | None | None | None | None | N |
| N/M | 0.3393 | likely_benign | 0.3683 | ambiguous | 0.49 | Stabilizing | 0.958 | D | 0.395 | neutral | None | None | None | None | N |
| N/P | 0.7476 | likely_pathogenic | 0.7143 | pathogenic | -0.098 | Destabilizing | 0.364 | N | 0.414 | neutral | None | None | None | None | N |
| N/Q | 0.2537 | likely_benign | 0.275 | benign | -0.373 | Destabilizing | 0.22 | N | 0.241 | neutral | None | None | None | None | N |
| N/R | 0.3297 | likely_benign | 0.3439 | ambiguous | 0.179 | Stabilizing | 0.22 | N | 0.263 | neutral | None | None | None | None | N |
| N/S | 0.0763 | likely_benign | 0.0774 | benign | -0.119 | Destabilizing | 0.042 | N | 0.356 | neutral | N | 0.504637139 | None | None | N |
| N/T | 0.1294 | likely_benign | 0.1372 | benign | -0.005 | Destabilizing | 0.081 | N | 0.241 | neutral | N | 0.473421656 | None | None | N |
| N/V | 0.2119 | likely_benign | 0.2252 | benign | -0.098 | Destabilizing | 0.364 | N | 0.458 | neutral | None | None | None | None | N |
| N/W | 0.779 | likely_pathogenic | 0.7866 | pathogenic | -0.719 | Destabilizing | 0.958 | D | 0.499 | neutral | None | None | None | None | N |
| N/Y | 0.1798 | likely_benign | 0.1806 | benign | -0.454 | Destabilizing | 0.822 | D | 0.413 | neutral | N | 0.493349564 | 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.