Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31413 | 94462;94463;94464 | chr2:178547288;178547287;178547286 | chr2:179412015;179412014;179412013 |
| N2AB | 29772 | 89539;89540;89541 | chr2:178547288;178547287;178547286 | chr2:179412015;179412014;179412013 |
| N2A | 28845 | 86758;86759;86760 | chr2:178547288;178547287;178547286 | chr2:179412015;179412014;179412013 |
| N2B | 22348 | 67267;67268;67269 | chr2:178547288;178547287;178547286 | chr2:179412015;179412014;179412013 |
| Novex-1 | 22473 | 67642;67643;67644 | chr2:178547288;178547287;178547286 | chr2:179412015;179412014;179412013 |
| Novex-2 | 22540 | 67843;67844;67845 | chr2:178547288;178547287;178547286 | chr2:179412015;179412014;179412013 |
| 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/A | rs1361033922  |
-0.794 | 0.64 | N | 0.494 | 0.163 | 0.233785782151 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.32E-05 | None | 0 | 0 | 0 |
| T/A | rs1361033922 |
-0.794 | 0.64 | N | 0.494 | 0.163 | 0.233785782151 | gnomAD-4.0.0 | 2.7443E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.65864E-05 | 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 | 0.0748 | likely_benign | 0.0816 | benign | -0.951 | Destabilizing | 0.64 | D | 0.494 | neutral | N | 0.456259694 | None | None | N |
| T/C | 0.3583 | ambiguous | 0.3887 | ambiguous | -0.614 | Destabilizing | 0.999 | D | 0.689 | prob.neutral | None | None | None | None | N |
| T/D | 0.6552 | likely_pathogenic | 0.717 | pathogenic | -0.984 | Destabilizing | 0.919 | D | 0.668 | neutral | None | None | None | None | N |
| T/E | 0.5846 | likely_pathogenic | 0.6291 | pathogenic | -0.915 | Destabilizing | 0.919 | D | 0.67 | neutral | None | None | None | None | N |
| T/F | 0.421 | ambiguous | 0.4656 | ambiguous | -0.705 | Destabilizing | 0.996 | D | 0.749 | deleterious | None | None | None | None | N |
| T/G | 0.132 | likely_benign | 0.1343 | benign | -1.287 | Destabilizing | 0.034 | N | 0.437 | neutral | None | None | None | None | N |
| T/H | 0.4175 | ambiguous | 0.4609 | ambiguous | -1.576 | Destabilizing | 0.999 | D | 0.731 | prob.delet. | None | None | None | None | N |
| T/I | 0.3992 | ambiguous | 0.3987 | ambiguous | -0.116 | Destabilizing | 0.984 | D | 0.72 | prob.delet. | N | 0.499493183 | None | None | N |
| T/K | 0.3885 | ambiguous | 0.4307 | ambiguous | -1.026 | Destabilizing | 0.976 | D | 0.668 | neutral | None | None | None | None | N |
| T/L | 0.1324 | likely_benign | 0.1423 | benign | -0.116 | Destabilizing | 0.919 | D | 0.661 | neutral | None | None | None | None | N |
| T/M | 0.1205 | likely_benign | 0.1325 | benign | 0.127 | Stabilizing | 0.999 | D | 0.692 | prob.neutral | None | None | None | None | N |
| T/N | 0.1869 | likely_benign | 0.1922 | benign | -1.17 | Destabilizing | 0.896 | D | 0.569 | neutral | N | 0.476981683 | None | None | N |
| T/P | 0.1326 | likely_benign | 0.1769 | benign | -0.362 | Destabilizing | 0.984 | D | 0.717 | prob.delet. | N | 0.488025396 | None | None | N |
| T/Q | 0.3277 | likely_benign | 0.3504 | ambiguous | -1.196 | Destabilizing | 0.988 | D | 0.718 | prob.delet. | None | None | None | None | N |
| T/R | 0.3438 | ambiguous | 0.3956 | ambiguous | -0.916 | Destabilizing | 0.976 | D | 0.716 | prob.delet. | None | None | None | None | N |
| T/S | 0.0928 | likely_benign | 0.1 | benign | -1.356 | Destabilizing | 0.103 | N | 0.292 | neutral | N | 0.419682818 | None | None | N |
| T/V | 0.2161 | likely_benign | 0.2216 | benign | -0.362 | Destabilizing | 0.919 | D | 0.585 | neutral | None | None | None | None | N |
| T/W | 0.7692 | likely_pathogenic | 0.8082 | pathogenic | -0.747 | Destabilizing | 0.999 | D | 0.745 | deleterious | None | None | None | None | N |
| T/Y | 0.4952 | ambiguous | 0.5338 | ambiguous | -0.502 | Destabilizing | 0.996 | D | 0.745 | deleterious | 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.