Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21914 | 65965;65966;65967 | chr2:178583063;178583062;178583061 | chr2:179447790;179447789;179447788 |
| N2AB | 20273 | 61042;61043;61044 | chr2:178583063;178583062;178583061 | chr2:179447790;179447789;179447788 |
| N2A | 19346 | 58261;58262;58263 | chr2:178583063;178583062;178583061 | chr2:179447790;179447789;179447788 |
| N2B | 12849 | 38770;38771;38772 | chr2:178583063;178583062;178583061 | chr2:179447790;179447789;179447788 |
| Novex-1 | 12974 | 39145;39146;39147 | chr2:178583063;178583062;178583061 | chr2:179447790;179447789;179447788 |
| Novex-2 | 13041 | 39346;39347;39348 | chr2:178583063;178583062;178583061 | chr2:179447790;179447789;179447788 |
| 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 | None | N | 0.291 | 0.223 | 0.385578977469 | gnomAD-4.0.0 | 6.85214E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16241E-05 | 0 |
| M/T | None | None | None | N | 0.29 | 0.165 | 0.415820034956 | gnomAD-4.0.0 | 6.85214E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16241E-05 | 0 |
| M/V | rs2048136288  |
None | 0.011 | N | 0.244 | 0.123 | 0.485920709088 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/V | rs2048136288 |
None | 0.011 | N | 0.244 | 0.123 | 0.485920709088 | gnomAD-4.0.0 | 6.5754E-06 | None | None | None | None | N | None | 0 | 6.54879E-05 | None | 0 | 0 | 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 | 0.258 | likely_benign | 0.2127 | benign | -0.583 | Destabilizing | 0.006 | N | 0.33 | neutral | None | None | None | None | N |
| M/C | 0.5964 | likely_pathogenic | 0.5541 | ambiguous | -0.289 | Destabilizing | 0.54 | D | 0.469 | neutral | None | None | None | None | N |
| M/D | 0.6649 | likely_pathogenic | 0.6503 | pathogenic | 0.138 | Stabilizing | 0.064 | N | 0.529 | neutral | None | None | None | None | N |
| M/E | 0.3409 | ambiguous | 0.3201 | benign | 0.079 | Stabilizing | 0.006 | N | 0.449 | neutral | None | None | None | None | N |
| M/F | 0.2306 | likely_benign | 0.2217 | benign | -0.284 | Destabilizing | 0.251 | N | 0.404 | neutral | None | None | None | None | N |
| M/G | 0.4533 | ambiguous | 0.3863 | ambiguous | -0.757 | Destabilizing | 0.029 | N | 0.491 | neutral | None | None | None | None | N |
| M/H | 0.3594 | ambiguous | 0.3129 | benign | 0.017 | Stabilizing | 0.54 | D | 0.545 | neutral | None | None | None | None | N |
| M/I | 0.2408 | likely_benign | 0.2084 | benign | -0.215 | Destabilizing | 0.025 | N | 0.352 | neutral | N | 0.421792909 | None | None | N |
| M/K | 0.1437 | likely_benign | 0.1227 | benign | 0.312 | Stabilizing | None | N | 0.291 | neutral | N | 0.423811707 | None | None | N |
| M/L | 0.1087 | likely_benign | 0.1037 | benign | -0.215 | Destabilizing | 0.005 | N | 0.247 | neutral | N | 0.402495072 | None | None | N |
| M/N | 0.3246 | likely_benign | 0.2977 | benign | 0.528 | Stabilizing | 0.064 | N | 0.515 | neutral | None | None | None | None | N |
| M/P | 0.5768 | likely_pathogenic | 0.5227 | ambiguous | -0.31 | Destabilizing | 0.121 | N | 0.522 | neutral | None | None | None | None | N |
| M/Q | 0.1684 | likely_benign | 0.1437 | benign | 0.336 | Stabilizing | 0.001 | N | 0.197 | neutral | None | None | None | None | N |
| M/R | 0.1522 | likely_benign | 0.1281 | benign | 0.829 | Stabilizing | None | N | 0.291 | neutral | N | 0.426121293 | None | None | N |
| M/S | 0.2593 | likely_benign | 0.2144 | benign | 0.085 | Stabilizing | 0.006 | N | 0.36 | neutral | None | None | None | None | N |
| M/T | 0.1244 | likely_benign | 0.099 | benign | 0.125 | Stabilizing | None | N | 0.29 | neutral | N | 0.402687073 | None | None | N |
| M/V | 0.0742 | likely_benign | 0.0673 | benign | -0.31 | Destabilizing | 0.011 | N | 0.244 | neutral | N | 0.378847421 | None | None | N |
| M/W | 0.5321 | ambiguous | 0.5082 | ambiguous | -0.245 | Destabilizing | 0.781 | D | 0.476 | neutral | None | None | None | None | N |
| M/Y | 0.4349 | ambiguous | 0.4363 | ambiguous | -0.111 | Destabilizing | 0.251 | N | 0.466 | 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.