Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34143 | 102652;102653;102654 | chr2:178534188;178534187;178534186 | chr2:179398915;179398914;179398913 |
| N2AB | 32502 | 97729;97730;97731 | chr2:178534188;178534187;178534186 | chr2:179398915;179398914;179398913 |
| N2A | 31575 | 94948;94949;94950 | chr2:178534188;178534187;178534186 | chr2:179398915;179398914;179398913 |
| N2B | 25078 | 75457;75458;75459 | chr2:178534188;178534187;178534186 | chr2:179398915;179398914;179398913 |
| Novex-1 | 25203 | 75832;75833;75834 | chr2:178534188;178534187;178534186 | chr2:179398915;179398914;179398913 |
| Novex-2 | 25270 | 76033;76034;76035 | chr2:178534188;178534187;178534186 | chr2:179398915;179398914;179398913 |
| 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/K | None | None | 0.003 | N | 0.129 | 0.349 | 0.684588293173 | gnomAD-4.0.0 | 6.84154E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.51902E-05 | None | 0 | 0 | 0 | 0 | 0 |
| M/L | rs371226574  |
0.003 | 0.047 | N | 0.148 | 0.19 | 0.523185410202 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/L | rs371226574 |
0.003 | 0.047 | N | 0.148 | 0.19 | 0.523185410202 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 2.41E-05 | 1.30993E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 9.56023E-04 |
| M/L | rs371226574 |
0.003 | 0.047 | N | 0.148 | 0.19 | 0.523185410202 | gnomAD-4.0.0 | 1.15283E-05 | None | None | None | None | I | None | 1.69182E-05 | 6.77943E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.13746E-04 |
| M/T | rs397517786 |
0.306 | 0.001 | N | 0.13 | 0.304 | 0.722392329672 | gnomAD-2.1.1 | 7.85E-05 | None | None | None | None | I | None | 4.13E-05 | 5.66E-05 | None | 0 | 0 | None | 0 | None | 7.99E-05 | 1.32552E-04 | 0 |
| M/T | rs397517786 |
0.306 | 0.001 | N | 0.13 | 0.304 | 0.722392329672 | gnomAD-3.1.2 | 9.2E-05 | None | None | None | None | I | None | 2.41E-05 | 6.54E-05 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 1.47011E-04 | 2.06868E-04 | 0 |
| M/T | rs397517786 |
0.306 | 0.001 | N | 0.13 | 0.304 | 0.722392329672 | gnomAD-4.0.0 | 1.21451E-04 | None | None | None | None | I | None | 1.33522E-05 | 4.99967E-05 | None | 0 | 0 | None | 3.12422E-05 | 1.64366E-04 | 1.55103E-04 | 1.09779E-05 | 8.00461E-05 |
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 | 0.3423 | ambiguous | 0.361 | ambiguous | -1.072 | Destabilizing | 0.061 | N | 0.25 | neutral | None | None | None | None | I |
| M/C | 0.7413 | likely_pathogenic | 0.7567 | pathogenic | -0.244 | Destabilizing | 0.94 | D | 0.301 | neutral | None | None | None | None | I |
| M/D | 0.71 | likely_pathogenic | 0.7089 | pathogenic | -0.168 | Destabilizing | 0.418 | N | 0.4 | neutral | None | None | None | None | I |
| M/E | 0.3121 | likely_benign | 0.3268 | benign | -0.196 | Destabilizing | 0.228 | N | 0.351 | neutral | None | None | None | None | I |
| M/F | 0.3624 | ambiguous | 0.3474 | ambiguous | -0.54 | Destabilizing | 0.418 | N | 0.245 | neutral | None | None | None | None | I |
| M/G | 0.5285 | ambiguous | 0.5327 | ambiguous | -1.275 | Destabilizing | 0.228 | N | 0.362 | neutral | None | None | None | None | I |
| M/H | 0.4259 | ambiguous | 0.4141 | ambiguous | -0.41 | Destabilizing | 0.94 | D | 0.286 | neutral | None | None | None | None | I |
| M/I | 0.354 | ambiguous | 0.3848 | ambiguous | -0.595 | Destabilizing | 0.101 | N | 0.247 | neutral | N | 0.467141196 | None | None | I |
| M/K | 0.1319 | likely_benign | 0.1413 | benign | -0.067 | Destabilizing | 0.003 | N | 0.129 | neutral | N | 0.394198089 | None | None | I |
| M/L | 0.1427 | likely_benign | 0.1443 | benign | -0.595 | Destabilizing | 0.047 | N | 0.148 | neutral | N | 0.418925962 | None | None | I |
| M/N | 0.4095 | ambiguous | 0.3779 | ambiguous | 0.208 | Stabilizing | 0.418 | N | 0.387 | neutral | None | None | None | None | I |
| M/P | 0.8488 | likely_pathogenic | 0.8203 | pathogenic | -0.729 | Destabilizing | 0.593 | D | 0.385 | neutral | None | None | None | None | I |
| M/Q | 0.1661 | likely_benign | 0.1558 | benign | 0.046 | Stabilizing | 0.418 | N | 0.241 | neutral | None | None | None | None | I |
| M/R | 0.1556 | likely_benign | 0.1547 | benign | 0.465 | Stabilizing | 0.213 | N | 0.341 | neutral | N | 0.366110197 | None | None | I |
| M/S | 0.2813 | likely_benign | 0.2756 | benign | -0.241 | Destabilizing | 0.129 | N | 0.299 | neutral | None | None | None | None | I |
| M/T | 0.1403 | likely_benign | 0.1602 | benign | -0.178 | Destabilizing | 0.001 | N | 0.13 | neutral | N | 0.429276242 | None | None | I |
| M/V | 0.1105 | likely_benign | 0.1245 | benign | -0.729 | Destabilizing | 0.101 | N | 0.201 | neutral | N | 0.448382077 | None | None | I |
| M/W | 0.6446 | likely_pathogenic | 0.6414 | pathogenic | -0.468 | Destabilizing | 0.002 | N | 0.189 | neutral | None | None | None | None | I |
| M/Y | 0.5593 | ambiguous | 0.5464 | ambiguous | -0.426 | Destabilizing | 0.418 | N | 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.