Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32170 | 96733;96734;96735 | chr2:178543465;178543464;178543463 | chr2:179408192;179408191;179408190 |
| N2AB | 30529 | 91810;91811;91812 | chr2:178543465;178543464;178543463 | chr2:179408192;179408191;179408190 |
| N2A | 29602 | 89029;89030;89031 | chr2:178543465;178543464;178543463 | chr2:179408192;179408191;179408190 |
| N2B | 23105 | 69538;69539;69540 | chr2:178543465;178543464;178543463 | chr2:179408192;179408191;179408190 |
| Novex-1 | 23230 | 69913;69914;69915 | chr2:178543465;178543464;178543463 | chr2:179408192;179408191;179408190 |
| Novex-2 | 23297 | 70114;70115;70116 | chr2:178543465;178543464;178543463 | chr2:179408192;179408191;179408190 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1157303589  |
-1.104 | 0.005 | N | 0.167 | 0.075 | 0.385084120042 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs1157303589 |
-1.104 | 0.005 | N | 0.167 | 0.075 | 0.385084120042 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/A | rs1157303589 |
-1.104 | 0.005 | N | 0.167 | 0.075 | 0.385084120042 | gnomAD-4.0.0 | 6.40539E-06 | None | None | None | None | N | None | 3.38226E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 7.17879E-06 | 0 | 0 |
| V/I | None | None | None | N | 0.076 | 0.079 | 0.243972157842 | gnomAD-4.0.0 | 6.8425E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99491E-07 | 0 | 0 |
| V/L | rs1380085253 |
-0.392 | None | N | 0.076 | 0.055 | 0.21737058555 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| V/L | rs1380085253 |
-0.392 | None | N | 0.076 | 0.055 | 0.21737058555 | gnomAD-4.0.0 | 1.3685E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79898E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.0949 | likely_benign | 0.0916 | benign | -0.937 | Destabilizing | 0.005 | N | 0.167 | neutral | N | 0.490889556 | None | None | N |
| V/C | 0.5928 | likely_pathogenic | 0.5627 | ambiguous | -0.813 | Destabilizing | 0.628 | D | 0.321 | neutral | None | None | None | None | N |
| V/D | 0.3043 | likely_benign | 0.2925 | benign | -0.359 | Destabilizing | 0.038 | N | 0.333 | neutral | None | None | None | None | N |
| V/E | 0.2256 | likely_benign | 0.2139 | benign | -0.386 | Destabilizing | None | N | 0.088 | neutral | N | 0.437439073 | None | None | N |
| V/F | 0.1687 | likely_benign | 0.1529 | benign | -0.741 | Destabilizing | 0.214 | N | 0.38 | neutral | None | None | None | None | N |
| V/G | 0.1478 | likely_benign | 0.1442 | benign | -1.189 | Destabilizing | 0.055 | N | 0.335 | neutral | N | 0.476306309 | None | None | N |
| V/H | 0.3993 | ambiguous | 0.388 | ambiguous | -0.527 | Destabilizing | 0.628 | D | 0.341 | neutral | None | None | None | None | N |
| V/I | 0.0738 | likely_benign | 0.0696 | benign | -0.375 | Destabilizing | None | N | 0.076 | neutral | N | 0.434209554 | None | None | N |
| V/K | 0.255 | likely_benign | 0.249 | benign | -0.686 | Destabilizing | 0.001 | N | 0.147 | neutral | None | None | None | None | N |
| V/L | 0.1029 | likely_benign | 0.099 | benign | -0.375 | Destabilizing | None | N | 0.076 | neutral | N | 0.474920026 | None | None | N |
| V/M | 0.0987 | likely_benign | 0.0898 | benign | -0.474 | Destabilizing | 0.214 | N | 0.281 | neutral | None | None | None | None | N |
| V/N | 0.1552 | likely_benign | 0.1523 | benign | -0.556 | Destabilizing | 0.072 | N | 0.377 | neutral | None | None | None | None | N |
| V/P | 0.3306 | likely_benign | 0.3552 | ambiguous | -0.526 | Destabilizing | 0.136 | N | 0.355 | neutral | None | None | None | None | N |
| V/Q | 0.198 | likely_benign | 0.1894 | benign | -0.697 | Destabilizing | 0.072 | N | 0.356 | neutral | None | None | None | None | N |
| V/R | 0.2375 | likely_benign | 0.2302 | benign | -0.199 | Destabilizing | 0.038 | N | 0.358 | neutral | None | None | None | None | N |
| V/S | 0.1107 | likely_benign | 0.1098 | benign | -1.074 | Destabilizing | 0.016 | N | 0.261 | neutral | None | None | None | None | N |
| V/T | 0.0909 | likely_benign | 0.0879 | benign | -0.979 | Destabilizing | None | N | 0.083 | neutral | None | None | None | None | N |
| V/W | 0.7128 | likely_pathogenic | 0.6763 | pathogenic | -0.854 | Destabilizing | 0.864 | D | 0.335 | neutral | None | None | None | None | N |
| V/Y | 0.4691 | ambiguous | 0.4459 | ambiguous | -0.552 | Destabilizing | 0.356 | N | 0.365 | 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.