Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22272 | 67039;67040;67041 | chr2:178580565;178580564;178580563 | chr2:179445292;179445291;179445290 |
| N2AB | 20631 | 62116;62117;62118 | chr2:178580565;178580564;178580563 | chr2:179445292;179445291;179445290 |
| N2A | 19704 | 59335;59336;59337 | chr2:178580565;178580564;178580563 | chr2:179445292;179445291;179445290 |
| N2B | 13207 | 39844;39845;39846 | chr2:178580565;178580564;178580563 | chr2:179445292;179445291;179445290 |
| Novex-1 | 13332 | 40219;40220;40221 | chr2:178580565;178580564;178580563 | chr2:179445292;179445291;179445290 |
| Novex-2 | 13399 | 40420;40421;40422 | chr2:178580565;178580564;178580563 | chr2:179445292;179445291;179445290 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs1460711951  |
None | 0.97 | N | 0.43 | 0.176 | 0.542808479177 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/M | rs1460711951 |
None | 0.97 | N | 0.43 | 0.176 | 0.542808479177 | gnomAD-4.0.0 | 2.03001E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.40997E-06 | 0 | 0 |
| I/T | rs773998250 |
-0.664 | 0.822 | N | 0.358 | 0.304 | 0.638501922959 | gnomAD-2.1.1 | 2.03E-05 | None | None | None | None | I | None | 0 | 2.92E-05 | None | 0 | 0 | None | 0 | None | 0 | 3.59E-05 | 0 |
| I/T | rs773998250 |
-0.664 | 0.822 | N | 0.358 | 0.304 | 0.638501922959 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| I/T | rs773998250 |
-0.664 | 0.822 | N | 0.358 | 0.304 | 0.638501922959 | gnomAD-4.0.0 | 1.48854E-05 | None | None | None | None | I | None | 0 | 1.67012E-05 | None | 0 | 0 | None | 0 | 0 | 1.69607E-05 | 0 | 4.80939E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5421 | ambiguous | 0.5901 | pathogenic | -1.191 | Destabilizing | 0.559 | D | 0.35 | neutral | None | None | None | None | I |
| I/C | 0.6988 | likely_pathogenic | 0.751 | pathogenic | -0.911 | Destabilizing | 0.998 | D | 0.433 | neutral | None | None | None | None | I |
| I/D | 0.8477 | likely_pathogenic | 0.8694 | pathogenic | -0.534 | Destabilizing | 0.993 | D | 0.545 | neutral | None | None | None | None | I |
| I/E | 0.7004 | likely_pathogenic | 0.7189 | pathogenic | -0.531 | Destabilizing | 0.978 | D | 0.525 | neutral | None | None | None | None | I |
| I/F | 0.2888 | likely_benign | 0.3229 | benign | -0.708 | Destabilizing | 0.956 | D | 0.373 | neutral | None | None | None | None | I |
| I/G | 0.823 | likely_pathogenic | 0.8548 | pathogenic | -1.481 | Destabilizing | 0.978 | D | 0.471 | neutral | None | None | None | None | I |
| I/H | 0.5823 | likely_pathogenic | 0.6127 | pathogenic | -0.544 | Destabilizing | 0.998 | D | 0.558 | neutral | None | None | None | None | I |
| I/K | 0.5814 | likely_pathogenic | 0.6154 | pathogenic | -0.87 | Destabilizing | 0.97 | D | 0.529 | neutral | N | 0.494037009 | None | None | I |
| I/L | 0.1478 | likely_benign | 0.1662 | benign | -0.486 | Destabilizing | 0.294 | N | 0.226 | neutral | N | 0.465333042 | None | None | I |
| I/M | 0.1628 | likely_benign | 0.1807 | benign | -0.563 | Destabilizing | 0.97 | D | 0.43 | neutral | N | 0.49332772 | None | None | I |
| I/N | 0.3449 | ambiguous | 0.3751 | ambiguous | -0.808 | Destabilizing | 0.993 | D | 0.554 | neutral | None | None | None | None | I |
| I/P | 0.8862 | likely_pathogenic | 0.9047 | pathogenic | -0.689 | Destabilizing | 0.993 | D | 0.549 | neutral | None | None | None | None | I |
| I/Q | 0.5295 | ambiguous | 0.5536 | ambiguous | -0.924 | Destabilizing | 0.993 | D | 0.562 | neutral | None | None | None | None | I |
| I/R | 0.5165 | ambiguous | 0.5511 | ambiguous | -0.317 | Destabilizing | 0.97 | D | 0.56 | neutral | N | 0.478011551 | None | None | I |
| I/S | 0.3985 | ambiguous | 0.4373 | ambiguous | -1.387 | Destabilizing | 0.978 | D | 0.425 | neutral | None | None | None | None | I |
| I/T | 0.2261 | likely_benign | 0.2461 | benign | -1.262 | Destabilizing | 0.822 | D | 0.358 | neutral | N | 0.421752836 | None | None | I |
| I/V | 0.0753 | likely_benign | 0.0816 | benign | -0.689 | Destabilizing | 0.002 | N | 0.156 | neutral | N | 0.41253592 | None | None | I |
| I/W | 0.9032 | likely_pathogenic | 0.9164 | pathogenic | -0.77 | Destabilizing | 0.998 | D | 0.651 | neutral | None | None | None | None | I |
| I/Y | 0.6253 | likely_pathogenic | 0.6546 | pathogenic | -0.542 | Destabilizing | 0.978 | D | 0.418 | 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.