Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8598 | 26017;26018;26019 | chr2:178715622;178715621;178715620 | chr2:179580349;179580348;179580347 |
| N2AB | 8281 | 25066;25067;25068 | chr2:178715622;178715621;178715620 | chr2:179580349;179580348;179580347 |
| N2A | 7354 | 22285;22286;22287 | chr2:178715622;178715621;178715620 | chr2:179580349;179580348;179580347 |
| 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 | rs770947302  |
-0.061 | None | N | 0.096 | 0.132 | 0.433157607263 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.11483E-04 | None | 3.27E-05 | None | 0 | 0 | 0 |
| M/I | rs770947302 |
-0.061 | None | N | 0.096 | 0.132 | 0.433157607263 | gnomAD-4.0.0 | 3.18338E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.77346E-05 | None | 0 | 0 | 0 | 1.43308E-05 | 0 |
| M/T | None | None | None | D | 0.165 | 0.312 | 0.777005541942 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| M/V | rs1180662147 |
None | 0.003 | N | 0.205 | 0.177 | 0.423836183345 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/V | rs1180662147 |
None | 0.003 | N | 0.205 | 0.177 | 0.423836183345 | gnomAD-4.0.0 | 6.57393E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47016E-05 | 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 | 0.6353 | likely_pathogenic | 0.6316 | pathogenic | -2.287 | Highly Destabilizing | 0.043 | N | 0.277 | neutral | None | None | None | None | I |
| M/C | 0.8691 | likely_pathogenic | 0.8717 | pathogenic | -1.718 | Destabilizing | 0.844 | D | 0.479 | neutral | None | None | None | None | I |
| M/D | 0.9412 | likely_pathogenic | 0.9403 | pathogenic | -1.138 | Destabilizing | 0.132 | N | 0.549 | neutral | None | None | None | None | I |
| M/E | 0.7228 | likely_pathogenic | 0.7269 | pathogenic | -1.021 | Destabilizing | 0.058 | N | 0.47 | neutral | None | None | None | None | I |
| M/F | 0.366 | ambiguous | 0.356 | ambiguous | -0.956 | Destabilizing | 0.006 | N | 0.309 | neutral | None | None | None | None | I |
| M/G | 0.8066 | likely_pathogenic | 0.8133 | pathogenic | -2.694 | Highly Destabilizing | 0.337 | N | 0.431 | neutral | None | None | None | None | I |
| M/H | 0.6841 | likely_pathogenic | 0.6572 | pathogenic | -1.843 | Destabilizing | 0.693 | D | 0.474 | neutral | None | None | None | None | I |
| M/I | 0.3904 | ambiguous | 0.4079 | ambiguous | -1.171 | Destabilizing | None | N | 0.096 | neutral | N | 0.463522101 | None | None | I |
| M/K | 0.2627 | likely_benign | 0.263 | benign | -1.114 | Destabilizing | 0.066 | N | 0.412 | neutral | D | 0.522043105 | None | None | I |
| M/L | 0.1874 | likely_benign | 0.1884 | benign | -1.171 | Destabilizing | None | N | 0.047 | neutral | N | 0.474701887 | None | None | I |
| M/N | 0.7051 | likely_pathogenic | 0.7037 | pathogenic | -1.146 | Destabilizing | 0.132 | N | 0.534 | neutral | None | None | None | None | I |
| M/P | 0.9142 | likely_pathogenic | 0.9025 | pathogenic | -1.519 | Destabilizing | 0.317 | N | 0.539 | neutral | None | None | None | None | I |
| M/Q | 0.3687 | ambiguous | 0.3647 | ambiguous | -1.071 | Destabilizing | 0.391 | N | 0.417 | neutral | None | None | None | None | I |
| M/R | 0.2961 | likely_benign | 0.295 | benign | -0.791 | Destabilizing | 0.132 | N | 0.521 | neutral | N | 0.496950638 | None | None | I |
| M/S | 0.619 | likely_pathogenic | 0.6208 | pathogenic | -1.813 | Destabilizing | 0.049 | N | 0.353 | neutral | None | None | None | None | I |
| M/T | 0.4225 | ambiguous | 0.4217 | ambiguous | -1.572 | Destabilizing | None | N | 0.165 | neutral | D | 0.536137135 | None | None | I |
| M/V | 0.1607 | likely_benign | 0.1663 | benign | -1.519 | Destabilizing | 0.003 | N | 0.205 | neutral | N | 0.489359121 | None | None | I |
| M/W | 0.7307 | likely_pathogenic | 0.7103 | pathogenic | -0.994 | Destabilizing | 0.968 | D | 0.465 | neutral | None | None | None | None | I |
| M/Y | 0.655 | likely_pathogenic | 0.641 | pathogenic | -1.058 | Destabilizing | 0.498 | N | 0.56 | 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.