Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24769 | 74530;74531;74532 | chr2:178571827;178571826;178571825 | chr2:179436554;179436553;179436552 |
| N2AB | 23128 | 69607;69608;69609 | chr2:178571827;178571826;178571825 | chr2:179436554;179436553;179436552 |
| N2A | 22201 | 66826;66827;66828 | chr2:178571827;178571826;178571825 | chr2:179436554;179436553;179436552 |
| N2B | 15704 | 47335;47336;47337 | chr2:178571827;178571826;178571825 | chr2:179436554;179436553;179436552 |
| Novex-1 | 15829 | 47710;47711;47712 | chr2:178571827;178571826;178571825 | chr2:179436554;179436553;179436552 |
| Novex-2 | 15896 | 47911;47912;47913 | chr2:178571827;178571826;178571825 | chr2:179436554;179436553;179436552 |
| 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 | rs372787601  |
0.165 | 0.042 | N | 0.281 | 0.188 | None | gnomAD-2.1.1 | 8.05E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.51426E-04 | 1.66168E-04 |
| N/D | rs372787601 |
0.165 | 0.042 | N | 0.281 | 0.188 | None | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 8.83E-05 | 2.07039E-04 | 4.77555E-04 |
| N/D | rs372787601 |
0.165 | 0.042 | N | 0.281 | 0.188 | None | gnomAD-4.0.0 | 6.13541E-05 | None | None | None | None | N | None | 3.99861E-05 | 1.66667E-05 | None | 0 | 0 | None | 0 | 9.91736E-04 | 6.5275E-05 | 3.29395E-05 | 1.44065E-04 |
| N/S | rs1032887625 |
-0.3 | 0.001 | N | 0.138 | 0.114 | 0.187945064343 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| N/S | rs1032887625 |
-0.3 | 0.001 | N | 0.138 | 0.114 | 0.187945064343 | 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 |
| N/S | rs1032887625 |
-0.3 | 0.001 | N | 0.138 | 0.114 | 0.187945064343 | gnomAD-4.0.0 | 2.47915E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39092E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.1768 | likely_benign | 0.2057 | benign | -0.576 | Destabilizing | 0.055 | N | 0.502 | neutral | None | None | None | None | N |
| N/C | 0.2219 | likely_benign | 0.246 | benign | 0.241 | Stabilizing | 0.883 | D | 0.57 | neutral | None | None | None | None | N |
| N/D | 0.1431 | likely_benign | 0.1496 | benign | 0.147 | Stabilizing | 0.042 | N | 0.281 | neutral | N | 0.428969597 | None | None | N |
| N/E | 0.2634 | likely_benign | 0.2891 | benign | 0.147 | Stabilizing | 0.001 | N | 0.12 | neutral | None | None | None | None | N |
| N/F | 0.4262 | ambiguous | 0.4613 | ambiguous | -0.717 | Destabilizing | 0.667 | D | 0.581 | neutral | None | None | None | None | N |
| N/G | 0.2084 | likely_benign | 0.2251 | benign | -0.807 | Destabilizing | 0.055 | N | 0.281 | neutral | None | None | None | None | N |
| N/H | 0.1047 | likely_benign | 0.1052 | benign | -0.72 | Destabilizing | 0.602 | D | 0.449 | neutral | D | 0.529557879 | None | None | N |
| N/I | 0.1844 | likely_benign | 0.2128 | benign | -0.039 | Destabilizing | 0.427 | N | 0.566 | neutral | N | 0.486252669 | None | None | N |
| N/K | 0.1672 | likely_benign | 0.1808 | benign | -0.025 | Destabilizing | 0.001 | N | 0.131 | neutral | N | 0.448902152 | None | None | N |
| N/L | 0.2328 | likely_benign | 0.2598 | benign | -0.039 | Destabilizing | 0.22 | N | 0.537 | neutral | None | None | None | None | N |
| N/M | 0.2368 | likely_benign | 0.2561 | benign | 0.345 | Stabilizing | 0.859 | D | 0.535 | neutral | None | None | None | None | N |
| N/P | 0.6885 | likely_pathogenic | 0.7338 | pathogenic | -0.189 | Destabilizing | 0.497 | N | 0.523 | neutral | None | None | None | None | N |
| N/Q | 0.216 | likely_benign | 0.229 | benign | -0.522 | Destabilizing | 0.124 | N | 0.252 | neutral | None | None | None | None | N |
| N/R | 0.2096 | likely_benign | 0.2272 | benign | 0.01 | Stabilizing | None | N | 0.126 | neutral | None | None | None | None | N |
| N/S | 0.0899 | likely_benign | 0.0992 | benign | -0.393 | Destabilizing | 0.001 | N | 0.138 | neutral | N | 0.443149616 | None | None | N |
| N/T | 0.0908 | likely_benign | 0.1016 | benign | -0.227 | Destabilizing | 0.042 | N | 0.244 | neutral | N | 0.4315299 | None | None | N |
| N/V | 0.1924 | likely_benign | 0.2176 | benign | -0.189 | Destabilizing | 0.22 | N | 0.543 | neutral | None | None | None | None | N |
| N/W | 0.6161 | likely_pathogenic | 0.6469 | pathogenic | -0.588 | Destabilizing | 0.958 | D | 0.599 | neutral | None | None | None | None | N |
| N/Y | 0.1279 | likely_benign | 0.1383 | benign | -0.372 | Destabilizing | 0.602 | D | 0.559 | neutral | N | 0.513396348 | 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.