Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23583 | 70972;70973;70974 | chr2:178575385;178575384;178575383 | chr2:179440112;179440111;179440110 |
| N2AB | 21942 | 66049;66050;66051 | chr2:178575385;178575384;178575383 | chr2:179440112;179440111;179440110 |
| N2A | 21015 | 63268;63269;63270 | chr2:178575385;178575384;178575383 | chr2:179440112;179440111;179440110 |
| N2B | 14518 | 43777;43778;43779 | chr2:178575385;178575384;178575383 | chr2:179440112;179440111;179440110 |
| Novex-1 | 14643 | 44152;44153;44154 | chr2:178575385;178575384;178575383 | chr2:179440112;179440111;179440110 |
| Novex-2 | 14710 | 44353;44354;44355 | chr2:178575385;178575384;178575383 | chr2:179440112;179440111;179440110 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs397517687  |
None | 0.171 | N | 0.494 | 0.174 | 0.316494231283 | gnomAD-4.0.0 | 6.84289E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65678E-05 |
| T/K | rs397517687 |
-0.751 | None | N | 0.257 | 0.213 | 0.270447802918 | gnomAD-2.1.1 | 4.02E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 8E-05 | 0 |
| T/K | rs397517687 |
-0.751 | None | N | 0.257 | 0.213 | 0.270447802918 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| T/K | rs397517687 |
-0.751 | None | N | 0.257 | 0.213 | 0.270447802918 | gnomAD-4.0.0 | 2.47906E-05 | None | None | None | None | N | None | 0 | 3.33378E-05 | None | 0 | 0 | None | 0 | 3.28947E-04 | 2.54305E-05 | 5.48956E-05 | 1.60128E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0749 | likely_benign | 0.0722 | benign | -0.632 | Destabilizing | None | N | 0.155 | neutral | N | 0.430441317 | None | None | N |
| T/C | 0.2767 | likely_benign | 0.2721 | benign | -0.397 | Destabilizing | 0.676 | D | 0.444 | neutral | None | None | None | None | N |
| T/D | 0.4009 | ambiguous | 0.3991 | ambiguous | -0.113 | Destabilizing | None | N | 0.268 | neutral | None | None | None | None | N |
| T/E | 0.3855 | ambiguous | 0.3851 | ambiguous | -0.106 | Destabilizing | 0.016 | N | 0.442 | neutral | None | None | None | None | N |
| T/F | 0.3554 | ambiguous | 0.3204 | benign | -0.666 | Destabilizing | 0.356 | N | 0.491 | neutral | None | None | None | None | N |
| T/G | 0.1808 | likely_benign | 0.1802 | benign | -0.895 | Destabilizing | None | N | 0.281 | neutral | None | None | None | None | N |
| T/H | 0.3112 | likely_benign | 0.3063 | benign | -1.086 | Destabilizing | 0.356 | N | 0.479 | neutral | None | None | None | None | N |
| T/I | 0.2842 | likely_benign | 0.2624 | benign | -0.027 | Destabilizing | 0.171 | N | 0.494 | neutral | N | 0.508304667 | None | None | N |
| T/K | 0.3114 | likely_benign | 0.3231 | benign | -0.717 | Destabilizing | None | N | 0.257 | neutral | N | 0.493951291 | None | None | N |
| T/L | 0.1374 | likely_benign | 0.1247 | benign | -0.027 | Destabilizing | 0.072 | N | 0.435 | neutral | None | None | None | None | N |
| T/M | 0.1122 | likely_benign | 0.106 | benign | 0.068 | Stabilizing | 0.628 | D | 0.462 | neutral | None | None | None | None | N |
| T/N | 0.1352 | likely_benign | 0.131 | benign | -0.669 | Destabilizing | 0.038 | N | 0.331 | neutral | None | None | None | None | N |
| T/P | 0.5967 | likely_pathogenic | 0.5588 | ambiguous | -0.196 | Destabilizing | 0.055 | N | 0.463 | neutral | N | 0.469739851 | None | None | N |
| T/Q | 0.2543 | likely_benign | 0.2626 | benign | -0.753 | Destabilizing | 0.214 | N | 0.496 | neutral | None | None | None | None | N |
| T/R | 0.2716 | likely_benign | 0.2726 | benign | -0.487 | Destabilizing | 0.029 | N | 0.461 | neutral | N | 0.48937219 | None | None | N |
| T/S | 0.0908 | likely_benign | 0.0864 | benign | -0.911 | Destabilizing | None | N | 0.168 | neutral | N | 0.439596731 | None | None | N |
| T/V | 0.1878 | likely_benign | 0.1777 | benign | -0.196 | Destabilizing | 0.072 | N | 0.337 | neutral | None | None | None | None | N |
| T/W | 0.7274 | likely_pathogenic | 0.7047 | pathogenic | -0.675 | Destabilizing | 0.864 | D | 0.516 | neutral | None | None | None | None | N |
| T/Y | 0.3669 | ambiguous | 0.3375 | benign | -0.429 | Destabilizing | 0.356 | N | 0.497 | 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.