Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31339 | 94240;94241;94242 | chr2:178547611;178547610;178547609 | chr2:179412338;179412337;179412336 |
| N2AB | 29698 | 89317;89318;89319 | chr2:178547611;178547610;178547609 | chr2:179412338;179412337;179412336 |
| N2A | 28771 | 86536;86537;86538 | chr2:178547611;178547610;178547609 | chr2:179412338;179412337;179412336 |
| N2B | 22274 | 67045;67046;67047 | chr2:178547611;178547610;178547609 | chr2:179412338;179412337;179412336 |
| Novex-1 | 22399 | 67420;67421;67422 | chr2:178547611;178547610;178547609 | chr2:179412338;179412337;179412336 |
| Novex-2 | 22466 | 67621;67622;67623 | chr2:178547611;178547610;178547609 | chr2:179412338;179412337;179412336 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs184078016  |
-0.35 | 0.991 | N | 0.667 | 0.244 | None | gnomAD-2.1.1 | 3.07081E-04 | None | None | None | None | I | None | 0 | 0 | None | 0 | 4.30504E-03 | None | 3.27E-05 | None | 0 | 0 | 1.40371E-04 |
| T/I | rs184078016 |
-0.35 | 0.991 | N | 0.667 | 0.244 | None | gnomAD-3.1.2 | 1.11741E-04 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 3.28185E-03 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs184078016 |
-0.35 | 0.991 | N | 0.667 | 0.244 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 3E-03 | 0 | None | None | None | 0 | None |
| T/I | rs184078016 |
-0.35 | 0.991 | N | 0.667 | 0.244 | None | gnomAD-4.0.0 | 1.87128E-04 | None | None | None | None | I | None | 0 | 0 | None | 0 | 6.55372E-03 | None | 0 | 0 | 0 | 1.09786E-05 | 1.12039E-04 |
| T/S | None | None | 0.079 | N | 0.395 | 0.196 | 0.0986583533028 | gnomAD-4.0.0 | 6.84177E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99441E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1043 | likely_benign | 0.0904 | benign | -0.994 | Destabilizing | 0.76 | D | 0.637 | neutral | N | 0.414159568 | None | None | I |
| T/C | 0.4066 | ambiguous | 0.3238 | benign | -0.552 | Destabilizing | 0.999 | D | 0.651 | neutral | None | None | None | None | I |
| T/D | 0.6736 | likely_pathogenic | 0.5391 | ambiguous | 0.205 | Stabilizing | 0.953 | D | 0.648 | neutral | None | None | None | None | I |
| T/E | 0.6405 | likely_pathogenic | 0.5303 | ambiguous | 0.199 | Stabilizing | 0.953 | D | 0.653 | neutral | None | None | None | None | I |
| T/F | 0.5565 | ambiguous | 0.4528 | ambiguous | -1.164 | Destabilizing | 0.998 | D | 0.707 | prob.neutral | None | None | None | None | I |
| T/G | 0.2757 | likely_benign | 0.2027 | benign | -1.227 | Destabilizing | 0.91 | D | 0.623 | neutral | None | None | None | None | I |
| T/H | 0.569 | likely_pathogenic | 0.4577 | ambiguous | -1.415 | Destabilizing | 0.999 | D | 0.703 | prob.neutral | None | None | None | None | I |
| T/I | 0.4918 | ambiguous | 0.4185 | ambiguous | -0.468 | Destabilizing | 0.991 | D | 0.667 | neutral | N | 0.512246263 | None | None | I |
| T/K | 0.6631 | likely_pathogenic | 0.5635 | ambiguous | -0.592 | Destabilizing | 0.953 | D | 0.65 | neutral | None | None | None | None | I |
| T/L | 0.234 | likely_benign | 0.1865 | benign | -0.468 | Destabilizing | 0.953 | D | 0.635 | neutral | None | None | None | None | I |
| T/M | 0.1219 | likely_benign | 0.125 | benign | -0.202 | Destabilizing | 0.999 | D | 0.646 | neutral | None | None | None | None | I |
| T/N | 0.2522 | likely_benign | 0.1709 | benign | -0.492 | Destabilizing | 0.939 | D | 0.699 | prob.neutral | D | 0.522847258 | None | None | I |
| T/P | 0.6473 | likely_pathogenic | 0.5004 | ambiguous | -0.612 | Destabilizing | 0.991 | D | 0.667 | neutral | N | 0.476306309 | None | None | I |
| T/Q | 0.5259 | ambiguous | 0.439 | ambiguous | -0.642 | Destabilizing | 0.993 | D | 0.652 | neutral | None | None | None | None | I |
| T/R | 0.5693 | likely_pathogenic | 0.4887 | ambiguous | -0.374 | Destabilizing | 0.986 | D | 0.662 | neutral | None | None | None | None | I |
| T/S | 0.1124 | likely_benign | 0.0915 | benign | -0.861 | Destabilizing | 0.079 | N | 0.395 | neutral | N | 0.372272874 | None | None | I |
| T/V | 0.2965 | likely_benign | 0.2563 | benign | -0.612 | Destabilizing | 0.953 | D | 0.669 | neutral | None | None | None | None | I |
| T/W | 0.8436 | likely_pathogenic | 0.7715 | pathogenic | -1.046 | Destabilizing | 0.999 | D | 0.739 | prob.delet. | None | None | None | None | I |
| T/Y | 0.6293 | likely_pathogenic | 0.4914 | ambiguous | -0.825 | Destabilizing | 0.998 | D | 0.7 | prob.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.