Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27977 | 84154;84155;84156 | chr2:178562203;178562202;178562201 | chr2:179426930;179426929;179426928 |
| N2AB | 26336 | 79231;79232;79233 | chr2:178562203;178562202;178562201 | chr2:179426930;179426929;179426928 |
| N2A | 25409 | 76450;76451;76452 | chr2:178562203;178562202;178562201 | chr2:179426930;179426929;179426928 |
| N2B | 18912 | 56959;56960;56961 | chr2:178562203;178562202;178562201 | chr2:179426930;179426929;179426928 |
| Novex-1 | 19037 | 57334;57335;57336 | chr2:178562203;178562202;178562201 | chr2:179426930;179426929;179426928 |
| Novex-2 | 19104 | 57535;57536;57537 | chr2:178562203;178562202;178562201 | chr2:179426930;179426929;179426928 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs1408743054  |
-0.059 | None | N | 0.258 | 0.142 | 0.0762999501168 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| R/G | rs1408743054 |
-0.059 | None | N | 0.258 | 0.142 | 0.0762999501168 | gnomAD-4.0.0 | 1.59389E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86116E-06 | 0 | 0 |
| R/T | rs1703931873 |
None | None | N | 0.287 | 0.113 | 0.267299060538 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06868E-04 | 0 |
| R/T | rs1703931873 |
None | None | N | 0.287 | 0.113 | 0.267299060538 | gnomAD-4.0.0 | 6.57341E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.06868E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.1875 | likely_benign | 0.1841 | benign | 0.046 | Stabilizing | 0.007 | N | 0.371 | neutral | None | None | None | None | N |
| R/C | 0.1606 | likely_benign | 0.1388 | benign | -0.082 | Destabilizing | 0.676 | D | 0.435 | neutral | None | None | None | None | N |
| R/D | 0.3207 | likely_benign | 0.3094 | benign | -0.155 | Destabilizing | 0.016 | N | 0.428 | neutral | None | None | None | None | N |
| R/E | 0.2094 | likely_benign | 0.1964 | benign | -0.104 | Destabilizing | 0.016 | N | 0.405 | neutral | None | None | None | None | N |
| R/F | 0.4782 | ambiguous | 0.4408 | ambiguous | -0.204 | Destabilizing | 0.356 | N | 0.431 | neutral | None | None | None | None | N |
| R/G | 0.0477 | likely_benign | 0.0531 | benign | -0.128 | Destabilizing | None | N | 0.258 | neutral | N | 0.230427041 | None | None | N |
| R/H | 0.1021 | likely_benign | 0.095 | benign | -0.61 | Destabilizing | 0.214 | N | 0.406 | neutral | None | None | None | None | N |
| R/I | 0.3593 | ambiguous | 0.3274 | benign | 0.464 | Stabilizing | 0.029 | N | 0.451 | neutral | N | 0.430663108 | None | None | N |
| R/K | 0.0725 | likely_benign | 0.0682 | benign | -0.032 | Destabilizing | None | N | 0.248 | neutral | N | 0.437781082 | None | None | N |
| R/L | 0.222 | likely_benign | 0.2136 | benign | 0.464 | Stabilizing | 0.016 | N | 0.418 | neutral | None | None | None | None | N |
| R/M | 0.2181 | likely_benign | 0.2014 | benign | 0.066 | Stabilizing | 0.356 | N | 0.471 | neutral | None | None | None | None | N |
| R/N | 0.2254 | likely_benign | 0.2129 | benign | 0.192 | Stabilizing | None | N | 0.255 | neutral | None | None | None | None | N |
| R/P | 0.5937 | likely_pathogenic | 0.6243 | pathogenic | 0.344 | Stabilizing | 0.136 | N | 0.451 | neutral | None | None | None | None | N |
| R/Q | 0.0919 | likely_benign | 0.0846 | benign | 0.091 | Stabilizing | 0.038 | N | 0.421 | neutral | None | None | None | None | N |
| R/S | 0.183 | likely_benign | 0.1754 | benign | -0.095 | Destabilizing | 0.005 | N | 0.417 | neutral | N | 0.42404378 | None | None | N |
| R/T | 0.1484 | likely_benign | 0.1427 | benign | 0.076 | Stabilizing | None | N | 0.287 | neutral | N | 0.448902152 | None | None | N |
| R/V | 0.3518 | ambiguous | 0.3313 | benign | 0.344 | Stabilizing | 0.016 | N | 0.461 | neutral | None | None | None | None | N |
| R/W | 0.2046 | likely_benign | 0.1989 | benign | -0.303 | Destabilizing | 0.864 | D | 0.426 | neutral | None | None | None | None | N |
| R/Y | 0.3219 | likely_benign | 0.2971 | benign | 0.105 | Stabilizing | 0.356 | N | 0.43 | 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.