Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8312 | 25159;25160;25161 | chr2:178718072;178718071;178718070 | chr2:179582799;179582798;179582797 |
| N2AB | 7995 | 24208;24209;24210 | chr2:178718072;178718071;178718070 | chr2:179582799;179582798;179582797 |
| N2A | 7068 | 21427;21428;21429 | chr2:178718072;178718071;178718070 | chr2:179582799;179582798;179582797 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | None | None | None | N | 0.111 | 0.115 | 0.385417323374 | gnomAD-4.0.0 | 1.59157E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85871E-06 | 0 | 0 |
| M/T | rs756314449  |
-1.101 | 0.001 | N | 0.223 | 0.353 | 0.788997730761 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| M/T | rs756314449 |
-1.101 | 0.001 | N | 0.223 | 0.353 | 0.788997730761 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07211E-04 | 0 |
| M/T | rs756314449 |
-1.101 | 0.001 | N | 0.223 | 0.353 | 0.788997730761 | gnomAD-4.0.0 | 5.12522E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 5.36049E-05 | 0 |
| M/V | rs777456359 |
-1.076 | 0.001 | N | 0.097 | 0.134 | 0.427368086475 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/V | rs777456359 |
-1.076 | 0.001 | N | 0.097 | 0.134 | 0.427368086475 | gnomAD-4.0.0 | 1.59155E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85869E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.8069 | likely_pathogenic | 0.862 | pathogenic | -2.012 | Highly Destabilizing | 0.123 | N | 0.333 | neutral | None | None | None | None | N |
| M/C | 0.9223 | likely_pathogenic | 0.9413 | pathogenic | -1.523 | Destabilizing | 0.88 | D | 0.525 | neutral | None | None | None | None | N |
| M/D | 0.9794 | likely_pathogenic | 0.986 | pathogenic | -0.705 | Destabilizing | 0.42 | N | 0.642 | neutral | None | None | None | None | N |
| M/E | 0.8817 | likely_pathogenic | 0.9087 | pathogenic | -0.596 | Destabilizing | 0.077 | N | 0.574 | neutral | None | None | None | None | N |
| M/F | 0.4835 | ambiguous | 0.4931 | ambiguous | -0.713 | Destabilizing | None | N | 0.149 | neutral | None | None | None | None | N |
| M/G | 0.9242 | likely_pathogenic | 0.9535 | pathogenic | -2.412 | Highly Destabilizing | 0.407 | N | 0.56 | neutral | None | None | None | None | N |
| M/H | 0.8716 | likely_pathogenic | 0.9106 | pathogenic | -1.538 | Destabilizing | 0.753 | D | 0.56 | neutral | None | None | None | None | N |
| M/I | 0.409 | ambiguous | 0.4011 | ambiguous | -0.928 | Destabilizing | None | N | 0.111 | neutral | N | 0.395104953 | None | None | N |
| M/K | 0.6555 | likely_pathogenic | 0.7269 | pathogenic | -0.79 | Destabilizing | 0.087 | N | 0.474 | neutral | N | 0.48484709 | None | None | N |
| M/L | 0.2231 | likely_benign | 0.2333 | benign | -0.928 | Destabilizing | None | N | 0.06 | neutral | N | 0.465274327 | None | None | N |
| M/N | 0.8456 | likely_pathogenic | 0.8906 | pathogenic | -0.8 | Destabilizing | 0.42 | N | 0.617 | neutral | None | None | None | None | N |
| M/P | 0.9396 | likely_pathogenic | 0.9562 | pathogenic | -1.264 | Destabilizing | 0.688 | D | 0.617 | neutral | None | None | None | None | N |
| M/Q | 0.6144 | likely_pathogenic | 0.6732 | pathogenic | -0.725 | Destabilizing | 0.753 | D | 0.473 | neutral | None | None | None | None | N |
| M/R | 0.6923 | likely_pathogenic | 0.761 | pathogenic | -0.519 | Destabilizing | 0.42 | N | 0.577 | neutral | N | 0.487240174 | None | None | N |
| M/S | 0.8128 | likely_pathogenic | 0.8782 | pathogenic | -1.485 | Destabilizing | 0.145 | N | 0.469 | neutral | None | None | None | None | N |
| M/T | 0.5561 | ambiguous | 0.6962 | pathogenic | -1.247 | Destabilizing | 0.001 | N | 0.223 | neutral | N | 0.500851125 | None | None | N |
| M/V | 0.1598 | likely_benign | 0.1778 | benign | -1.264 | Destabilizing | 0.001 | N | 0.097 | neutral | N | 0.436564786 | None | None | N |
| M/W | 0.8466 | likely_pathogenic | 0.8702 | pathogenic | -0.726 | Destabilizing | 0.976 | D | 0.513 | neutral | None | None | None | None | N |
| M/Y | 0.7812 | likely_pathogenic | 0.8228 | pathogenic | -0.763 | Destabilizing | 0.086 | N | 0.547 | 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.