Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13918 | 41977;41978;41979 | chr2:178635572;178635571;178635570 | chr2:179500299;179500298;179500297 |
| N2AB | 12277 | 37054;37055;37056 | chr2:178635572;178635571;178635570 | chr2:179500299;179500298;179500297 |
| N2A | 11350 | 34273;34274;34275 | chr2:178635572;178635571;178635570 | chr2:179500299;179500298;179500297 |
| N2B | 4853 | 14782;14783;14784 | chr2:178635572;178635571;178635570 | chr2:179500299;179500298;179500297 |
| Novex-1 | 4978 | 15157;15158;15159 | chr2:178635572;178635571;178635570 | chr2:179500299;179500298;179500297 |
| Novex-2 | 5045 | 15358;15359;15360 | chr2:178635572;178635571;178635570 | chr2:179500299;179500298;179500297 |
| 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 | rs2060334868  |
None | 0.011 | N | 0.409 | 0.126 | 0.130388298395 | gnomAD-4.0.0 | 3.46618E-06 | None | None | None | None | N | None | 9.00793E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 9.0812E-07 | 0 | 1.67482E-05 |
| N/K | rs1396769268 |
-0.127 | 0.011 | N | 0.336 | 0.021 | 0.0611884634855 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14784E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| N/K | rs1396769268 |
-0.127 | 0.011 | N | 0.336 | 0.021 | 0.0611884634855 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/K | rs1396769268 |
-0.127 | 0.011 | N | 0.336 | 0.021 | 0.0611884634855 | gnomAD-4.0.0 | 1.3152E-05 | None | None | None | None | N | None | 4.82532E-05 | 0 | 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 | 0.2798 | likely_benign | 0.3093 | benign | -0.345 | Destabilizing | 0.003 | N | 0.383 | neutral | None | None | None | None | N |
| N/C | 0.4173 | ambiguous | 0.4787 | ambiguous | 0.373 | Stabilizing | 0.204 | N | 0.499 | neutral | None | None | None | None | N |
| N/D | 0.1396 | likely_benign | 0.1391 | benign | 0.095 | Stabilizing | 0.011 | N | 0.409 | neutral | N | 0.443872049 | None | None | N |
| N/E | 0.6566 | likely_pathogenic | 0.6887 | pathogenic | 0.079 | Stabilizing | 0.015 | N | 0.339 | neutral | None | None | None | None | N |
| N/F | 0.7867 | likely_pathogenic | 0.8067 | pathogenic | -0.598 | Destabilizing | 0.204 | N | 0.587 | neutral | None | None | None | None | N |
| N/G | 0.2433 | likely_benign | 0.2476 | benign | -0.554 | Destabilizing | 0.015 | N | 0.319 | neutral | None | None | None | None | N |
| N/H | 0.3192 | likely_benign | 0.3576 | ambiguous | -0.583 | Destabilizing | 0.371 | N | 0.387 | neutral | N | 0.454663573 | None | None | N |
| N/I | 0.5598 | ambiguous | 0.5981 | pathogenic | 0.124 | Stabilizing | 0.013 | N | 0.501 | neutral | N | 0.455338525 | None | None | N |
| N/K | 0.6558 | likely_pathogenic | 0.6916 | pathogenic | 0.041 | Stabilizing | 0.011 | N | 0.336 | neutral | N | 0.442373446 | None | None | N |
| N/L | 0.3447 | ambiguous | 0.3641 | ambiguous | 0.124 | Stabilizing | 0.007 | N | 0.39 | neutral | None | None | None | None | N |
| N/M | 0.4482 | ambiguous | 0.4793 | ambiguous | 0.478 | Stabilizing | 0.204 | N | 0.49 | neutral | None | None | None | None | N |
| N/P | 0.881 | likely_pathogenic | 0.8888 | pathogenic | -0.004 | Destabilizing | 0.068 | N | 0.454 | neutral | None | None | None | None | N |
| N/Q | 0.6699 | likely_pathogenic | 0.704 | pathogenic | -0.399 | Destabilizing | 0.068 | N | 0.387 | neutral | None | None | None | None | N |
| N/R | 0.6911 | likely_pathogenic | 0.7241 | pathogenic | 0.051 | Stabilizing | 0.035 | N | 0.347 | neutral | None | None | None | None | N |
| N/S | 0.0735 | likely_benign | 0.0855 | benign | -0.209 | Destabilizing | None | N | 0.125 | neutral | N | 0.387934075 | None | None | N |
| N/T | 0.0687 | likely_benign | 0.0722 | benign | -0.071 | Destabilizing | None | N | 0.143 | neutral | N | 0.362287356 | None | None | N |
| N/V | 0.4262 | ambiguous | 0.476 | ambiguous | -0.004 | Destabilizing | 0.007 | N | 0.42 | neutral | None | None | None | None | N |
| N/W | 0.9399 | likely_pathogenic | 0.9522 | pathogenic | -0.551 | Destabilizing | 0.747 | D | 0.54 | neutral | None | None | None | None | N |
| N/Y | 0.5231 | ambiguous | 0.5755 | pathogenic | -0.299 | Destabilizing | 0.162 | N | 0.538 | neutral | N | 0.454663573 | 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.