Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31718 | 95377;95378;95379 | chr2:178546084;178546083;178546082 | chr2:179410811;179410810;179410809 |
| N2AB | 30077 | 90454;90455;90456 | chr2:178546084;178546083;178546082 | chr2:179410811;179410810;179410809 |
| N2A | 29150 | 87673;87674;87675 | chr2:178546084;178546083;178546082 | chr2:179410811;179410810;179410809 |
| N2B | 22653 | 68182;68183;68184 | chr2:178546084;178546083;178546082 | chr2:179410811;179410810;179410809 |
| Novex-1 | 22778 | 68557;68558;68559 | chr2:178546084;178546083;178546082 | chr2:179410811;179410810;179410809 |
| Novex-2 | 22845 | 68758;68759;68760 | chr2:178546084;178546083;178546082 | chr2:179410811;179410810;179410809 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/I | rs758006837  |
0.063 | 0.994 | N | 0.698 | 0.403 | None | gnomAD-2.1.1 | 2.88E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.32E-05 | 0 |
| S/I | rs758006837 |
0.063 | 0.994 | N | 0.698 | 0.403 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| S/I | rs758006837 |
0.063 | 0.994 | N | 0.698 | 0.403 | None | gnomAD-4.0.0 | 8.74991E-05 | None | None | None | None | N | None | 4.00588E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.10336E-04 | 0 | 1.28271E-04 |
| S/N | None | None | 0.4 | N | 0.268 | 0.219 | 0.242244723065 | gnomAD-4.0.0 | 6.85286E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00743E-07 | 0 | 0 |
| S/R | rs781462223 |
-0.151 | 0.997 | N | 0.617 | 0.589 | 0.476908202251 | gnomAD-2.1.1 | 5.27E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 4.27603E-04 | None | 0 | 0 | 0 |
| S/R | rs781462223 |
-0.151 | 0.997 | N | 0.617 | 0.589 | 0.476908202251 | gnomAD-4.0.0 | 6.85142E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00586E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.118 | likely_benign | 0.1247 | benign | -0.412 | Destabilizing | 0.964 | D | 0.544 | neutral | None | None | None | None | N |
| S/C | 0.1706 | likely_benign | 0.1824 | benign | -0.308 | Destabilizing | 1.0 | D | 0.628 | neutral | N | 0.49759425 | None | None | N |
| S/D | 0.5526 | ambiguous | 0.6081 | pathogenic | 0.151 | Stabilizing | 0.971 | D | 0.563 | neutral | None | None | None | None | N |
| S/E | 0.6309 | likely_pathogenic | 0.6955 | pathogenic | 0.067 | Stabilizing | 0.985 | D | 0.56 | neutral | None | None | None | None | N |
| S/F | 0.2509 | likely_benign | 0.2994 | benign | -0.922 | Destabilizing | 0.999 | D | 0.707 | prob.neutral | None | None | None | None | N |
| S/G | 0.1132 | likely_benign | 0.1222 | benign | -0.548 | Destabilizing | 0.98 | D | 0.594 | neutral | N | 0.48112261 | None | None | N |
| S/H | 0.4229 | ambiguous | 0.471 | ambiguous | -1.073 | Destabilizing | 0.999 | D | 0.632 | neutral | None | None | None | None | N |
| S/I | 0.2815 | likely_benign | 0.3229 | benign | -0.184 | Destabilizing | 0.994 | D | 0.698 | prob.neutral | N | 0.485197533 | None | None | N |
| S/K | 0.769 | likely_pathogenic | 0.8267 | pathogenic | -0.532 | Destabilizing | 0.985 | D | 0.565 | neutral | None | None | None | None | N |
| S/L | 0.1371 | likely_benign | 0.1547 | benign | -0.184 | Destabilizing | 0.985 | D | 0.591 | neutral | None | None | None | None | N |
| S/M | 0.2375 | likely_benign | 0.2509 | benign | 0.068 | Stabilizing | 1.0 | D | 0.613 | neutral | None | None | None | None | N |
| S/N | 0.1937 | likely_benign | 0.2217 | benign | -0.269 | Destabilizing | 0.4 | N | 0.268 | neutral | N | 0.483248977 | None | None | N |
| S/P | 0.8221 | likely_pathogenic | 0.8611 | pathogenic | -0.23 | Destabilizing | 0.999 | D | 0.623 | neutral | None | None | None | None | N |
| S/Q | 0.5625 | ambiguous | 0.6182 | pathogenic | -0.517 | Destabilizing | 0.998 | D | 0.584 | neutral | None | None | None | None | N |
| S/R | 0.73 | likely_pathogenic | 0.7457 | pathogenic | -0.341 | Destabilizing | 0.997 | D | 0.617 | neutral | N | 0.487501711 | None | None | N |
| S/T | 0.08 | likely_benign | 0.0849 | benign | -0.376 | Destabilizing | 0.4 | N | 0.231 | neutral | N | 0.434017553 | None | None | N |
| S/V | 0.2594 | likely_benign | 0.2893 | benign | -0.23 | Destabilizing | 0.996 | D | 0.607 | neutral | None | None | None | None | N |
| S/W | 0.4492 | ambiguous | 0.5212 | ambiguous | -0.911 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | N |
| S/Y | 0.2516 | likely_benign | 0.2902 | benign | -0.641 | Destabilizing | 0.999 | D | 0.702 | prob.neutral | None | None | 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.