Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17995 | 54208;54209;54210 | chr2:178605194;178605193;178605192 | chr2:179469921;179469920;179469919 |
| N2AB | 16354 | 49285;49286;49287 | chr2:178605194;178605193;178605192 | chr2:179469921;179469920;179469919 |
| N2A | 15427 | 46504;46505;46506 | chr2:178605194;178605193;178605192 | chr2:179469921;179469920;179469919 |
| N2B | 8930 | 27013;27014;27015 | chr2:178605194;178605193;178605192 | chr2:179469921;179469920;179469919 |
| Novex-1 | 9055 | 27388;27389;27390 | chr2:178605194;178605193;178605192 | chr2:179469921;179469920;179469919 |
| Novex-2 | 9122 | 27589;27590;27591 | chr2:178605194;178605193;178605192 | chr2:179469921;179469920;179469919 |
| 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 | 0.001 | N | 0.108 | 0.153 | 0.364342057095 | gnomAD-4.0.0 | 1.59456E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86331E-06 | 0 | 0 |
| M/K | rs1266231398  |
0.21 | 0.01 | N | 0.193 | 0.319 | 0.462461958149 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.49E-05 | 0 |
| M/K | rs1266231398 |
0.21 | 0.01 | N | 0.193 | 0.319 | 0.462461958149 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/K | rs1266231398 |
0.21 | 0.01 | N | 0.193 | 0.319 | 0.462461958149 | gnomAD-4.0.0 | 6.58432E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47275E-05 | 0 | 0 |
| M/V | rs754959032 |
-0.48 | 0.065 | N | 0.191 | 0.199 | 0.381580015636 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.98E-06 | 0 |
| M/V | rs754959032 |
-0.48 | 0.065 | N | 0.191 | 0.199 | 0.381580015636 | gnomAD-4.0.0 | 3.18919E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.58472E-05 | None | 0 | 0 | 0 | 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 | 0.6488 | likely_pathogenic | 0.6364 | pathogenic | -1.49 | Destabilizing | 0.495 | N | 0.383 | neutral | None | None | None | None | I |
| M/C | 0.8681 | likely_pathogenic | 0.883 | pathogenic | -1.274 | Destabilizing | 0.981 | D | 0.454 | neutral | None | None | None | None | I |
| M/D | 0.957 | likely_pathogenic | 0.9536 | pathogenic | -0.629 | Destabilizing | 0.828 | D | 0.526 | neutral | None | None | None | None | I |
| M/E | 0.8438 | likely_pathogenic | 0.8272 | pathogenic | -0.62 | Destabilizing | 0.704 | D | 0.457 | neutral | None | None | None | None | I |
| M/F | 0.3839 | ambiguous | 0.4739 | ambiguous | -0.712 | Destabilizing | 0.704 | D | 0.395 | neutral | None | None | None | None | I |
| M/G | 0.9168 | likely_pathogenic | 0.9156 | pathogenic | -1.78 | Destabilizing | 0.828 | D | 0.496 | neutral | None | None | None | None | I |
| M/H | 0.8083 | likely_pathogenic | 0.8308 | pathogenic | -0.958 | Destabilizing | 0.981 | D | 0.468 | neutral | None | None | None | None | I |
| M/I | 0.4999 | ambiguous | 0.5003 | ambiguous | -0.761 | Destabilizing | 0.001 | N | 0.108 | neutral | N | 0.403649865 | None | None | I |
| M/K | 0.4826 | ambiguous | 0.462 | ambiguous | -0.38 | Destabilizing | 0.01 | N | 0.193 | neutral | N | 0.40301236 | None | None | I |
| M/L | 0.1184 | likely_benign | 0.1291 | benign | -0.761 | Destabilizing | 0.065 | N | 0.134 | neutral | N | 0.384909389 | None | None | I |
| M/N | 0.7827 | likely_pathogenic | 0.7798 | pathogenic | -0.232 | Destabilizing | 0.828 | D | 0.501 | neutral | None | None | None | None | I |
| M/P | 0.7417 | likely_pathogenic | 0.7454 | pathogenic | -0.977 | Destabilizing | 0.936 | D | 0.495 | neutral | None | None | None | None | I |
| M/Q | 0.5537 | ambiguous | 0.5412 | ambiguous | -0.367 | Destabilizing | 0.704 | D | 0.406 | neutral | None | None | None | None | I |
| M/R | 0.5645 | likely_pathogenic | 0.5415 | ambiguous | 0.054 | Stabilizing | 0.473 | N | 0.419 | neutral | N | 0.420830117 | None | None | I |
| M/S | 0.7209 | likely_pathogenic | 0.7043 | pathogenic | -0.798 | Destabilizing | 0.495 | N | 0.417 | neutral | None | None | None | None | I |
| M/T | 0.6036 | likely_pathogenic | 0.5757 | pathogenic | -0.681 | Destabilizing | 0.425 | N | 0.414 | neutral | N | 0.397702541 | None | None | I |
| M/V | 0.1414 | likely_benign | 0.1398 | benign | -0.977 | Destabilizing | 0.065 | N | 0.191 | neutral | N | 0.434836777 | None | None | I |
| M/W | 0.7978 | likely_pathogenic | 0.8421 | pathogenic | -0.655 | Destabilizing | 0.995 | D | 0.449 | neutral | None | None | None | None | I |
| M/Y | 0.7278 | likely_pathogenic | 0.7781 | pathogenic | -0.611 | Destabilizing | 0.981 | D | 0.477 | 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.