Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7002 | 21229;21230;21231 | chr2:178724371;178724370;178724369 | chr2:179589098;179589097;179589096 |
| N2AB | 6685 | 20278;20279;20280 | chr2:178724371;178724370;178724369 | chr2:179589098;179589097;179589096 |
| N2A | 5758 | 17497;17498;17499 | chr2:178724371;178724370;178724369 | chr2:179589098;179589097;179589096 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs2078973512  |
None | 0.005 | N | 0.249 | 0.049 | 0.290962096972 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/L | rs2078973512 |
None | 0.005 | N | 0.249 | 0.049 | 0.290962096972 | gnomAD-4.0.0 | 6.57402E-06 | None | None | None | None | N | None | 2.41301E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/M | rs759813012 |
-0.559 | 0.171 | N | 0.463 | 0.056 | 0.458374381611 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| I/M | rs759813012 |
-0.559 | 0.171 | N | 0.463 | 0.056 | 0.458374381611 | gnomAD-4.0.0 | 1.36865E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79919E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.4568 | ambiguous | 0.3885 | ambiguous | -1.86 | Destabilizing | 0.007 | N | 0.319 | neutral | None | None | None | None | N |
| I/C | 0.7491 | likely_pathogenic | 0.7124 | pathogenic | -1.25 | Destabilizing | 0.356 | N | 0.533 | neutral | None | None | None | None | N |
| I/D | 0.6736 | likely_pathogenic | 0.6152 | pathogenic | -1.15 | Destabilizing | 0.072 | N | 0.565 | neutral | None | None | None | None | N |
| I/E | 0.5312 | ambiguous | 0.4815 | ambiguous | -1.066 | Destabilizing | 0.072 | N | 0.555 | neutral | None | None | None | None | N |
| I/F | 0.2059 | likely_benign | 0.1773 | benign | -1.152 | Destabilizing | 0.055 | N | 0.424 | neutral | N | 0.475590108 | None | None | N |
| I/G | 0.7122 | likely_pathogenic | 0.6559 | pathogenic | -2.266 | Highly Destabilizing | 0.031 | N | 0.507 | neutral | None | None | None | None | N |
| I/H | 0.4963 | ambiguous | 0.4415 | ambiguous | -1.524 | Destabilizing | 0.628 | D | 0.581 | neutral | None | None | None | None | N |
| I/K | 0.3452 | ambiguous | 0.3212 | benign | -1.129 | Destabilizing | 0.072 | N | 0.555 | neutral | None | None | None | None | N |
| I/L | 0.1595 | likely_benign | 0.153 | benign | -0.778 | Destabilizing | 0.005 | N | 0.249 | neutral | N | 0.441496177 | None | None | N |
| I/M | 0.1332 | likely_benign | 0.1195 | benign | -0.737 | Destabilizing | 0.171 | N | 0.463 | neutral | N | 0.478822414 | None | None | N |
| I/N | 0.2379 | likely_benign | 0.2044 | benign | -1.057 | Destabilizing | 0.055 | N | 0.589 | neutral | N | 0.426353367 | None | None | N |
| I/P | 0.9608 | likely_pathogenic | 0.9508 | pathogenic | -1.11 | Destabilizing | 0.136 | N | 0.61 | neutral | None | None | None | None | N |
| I/Q | 0.4264 | ambiguous | 0.3864 | ambiguous | -1.127 | Destabilizing | 0.356 | N | 0.625 | neutral | None | None | None | None | N |
| I/R | 0.2995 | likely_benign | 0.272 | benign | -0.719 | Destabilizing | 0.072 | N | 0.621 | neutral | None | None | None | None | N |
| I/S | 0.3197 | likely_benign | 0.2729 | benign | -1.814 | Destabilizing | None | N | 0.277 | neutral | N | 0.428700238 | None | None | N |
| I/T | 0.2497 | likely_benign | 0.2018 | benign | -1.601 | Destabilizing | None | N | 0.218 | neutral | N | 0.425833292 | None | None | N |
| I/V | 0.0899 | likely_benign | 0.0765 | benign | -1.11 | Destabilizing | None | N | 0.125 | neutral | N | 0.402439144 | None | None | N |
| I/W | 0.8052 | likely_pathogenic | 0.7775 | pathogenic | -1.282 | Destabilizing | 0.864 | D | 0.589 | neutral | None | None | None | None | N |
| I/Y | 0.4284 | ambiguous | 0.3997 | ambiguous | -1.025 | Destabilizing | 0.356 | N | 0.567 | 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.