Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17204 | 51835;51836;51837 | chr2:178609813;178609812;178609811 | chr2:179474540;179474539;179474538 |
| N2AB | 15563 | 46912;46913;46914 | chr2:178609813;178609812;178609811 | chr2:179474540;179474539;179474538 |
| N2A | 14636 | 44131;44132;44133 | chr2:178609813;178609812;178609811 | chr2:179474540;179474539;179474538 |
| N2B | 8139 | 24640;24641;24642 | chr2:178609813;178609812;178609811 | chr2:179474540;179474539;179474538 |
| Novex-1 | 8264 | 25015;25016;25017 | chr2:178609813;178609812;178609811 | chr2:179474540;179474539;179474538 |
| Novex-2 | 8331 | 25216;25217;25218 | chr2:178609813;178609812;178609811 | chr2:179474540;179474539;179474538 |
| 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/V | rs1383602491  |
-0.64 | None | N | 0.107 | 0.061 | 0.319402600006 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs1383602491 |
-0.64 | None | N | 0.107 | 0.061 | 0.319402600006 | gnomAD-4.0.0 | 1.8601E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54395E-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 | 0.2701 | likely_benign | 0.2358 | benign | -1.46 | Destabilizing | 0.035 | N | 0.294 | neutral | None | None | None | None | I |
| I/C | 0.6345 | likely_pathogenic | 0.6027 | pathogenic | -0.947 | Destabilizing | 0.555 | D | 0.345 | neutral | None | None | None | None | I |
| I/D | 0.6199 | likely_pathogenic | 0.5732 | pathogenic | -1.305 | Destabilizing | 0.555 | D | 0.406 | neutral | None | None | None | None | I |
| I/E | 0.5701 | likely_pathogenic | 0.5231 | ambiguous | -1.249 | Destabilizing | 0.555 | D | 0.393 | neutral | None | None | None | None | I |
| I/F | 0.1842 | likely_benign | 0.1725 | benign | -0.973 | Destabilizing | 0.117 | N | 0.299 | neutral | N | 0.440500808 | None | None | I |
| I/G | 0.421 | ambiguous | 0.3747 | ambiguous | -1.762 | Destabilizing | 0.262 | N | 0.379 | neutral | None | None | None | None | I |
| I/H | 0.5164 | ambiguous | 0.4855 | ambiguous | -0.713 | Destabilizing | 0.935 | D | 0.363 | neutral | None | None | None | None | I |
| I/K | 0.4822 | ambiguous | 0.4594 | ambiguous | -1.007 | Destabilizing | 0.262 | N | 0.394 | neutral | None | None | None | None | I |
| I/L | 0.0931 | likely_benign | 0.088 | benign | -0.682 | Destabilizing | None | N | 0.086 | neutral | N | 0.422915125 | None | None | I |
| I/M | 0.1023 | likely_benign | 0.0989 | benign | -0.743 | Destabilizing | 0.317 | N | 0.375 | neutral | N | 0.424261919 | None | None | I |
| I/N | 0.2189 | likely_benign | 0.1945 | benign | -1.14 | Destabilizing | 0.741 | D | 0.403 | neutral | N | 0.398728756 | None | None | I |
| I/P | 0.8781 | likely_pathogenic | 0.853 | pathogenic | -0.915 | Destabilizing | 0.555 | D | 0.413 | neutral | None | None | None | None | I |
| I/Q | 0.4408 | ambiguous | 0.4116 | ambiguous | -1.231 | Destabilizing | 0.791 | D | 0.393 | neutral | None | None | None | None | I |
| I/R | 0.4407 | ambiguous | 0.4178 | ambiguous | -0.457 | Destabilizing | 0.555 | D | 0.401 | neutral | None | None | None | None | I |
| I/S | 0.2245 | likely_benign | 0.2014 | benign | -1.634 | Destabilizing | 0.117 | N | 0.384 | neutral | N | 0.345030344 | None | None | I |
| I/T | 0.2366 | likely_benign | 0.2078 | benign | -1.458 | Destabilizing | 0.027 | N | 0.295 | neutral | N | 0.381545718 | None | None | I |
| I/V | 0.0667 | likely_benign | 0.0646 | benign | -0.915 | Destabilizing | None | N | 0.107 | neutral | N | 0.371198225 | None | None | I |
| I/W | 0.8354 | likely_pathogenic | 0.8234 | pathogenic | -1.07 | Destabilizing | 0.935 | D | 0.389 | neutral | None | None | None | None | I |
| I/Y | 0.5255 | ambiguous | 0.4887 | ambiguous | -0.812 | Destabilizing | 0.555 | D | 0.376 | neutral | None | None | None | None | I |
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.