Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29390 | 88393;88394;88395 | chr2:178556986;178556985;178556984 | chr2:179421713;179421712;179421711 |
| N2AB | 27749 | 83470;83471;83472 | chr2:178556986;178556985;178556984 | chr2:179421713;179421712;179421711 |
| N2A | 26822 | 80689;80690;80691 | chr2:178556986;178556985;178556984 | chr2:179421713;179421712;179421711 |
| N2B | 20325 | 61198;61199;61200 | chr2:178556986;178556985;178556984 | chr2:179421713;179421712;179421711 |
| Novex-1 | 20450 | 61573;61574;61575 | chr2:178556986;178556985;178556984 | chr2:179421713;179421712;179421711 |
| Novex-2 | 20517 | 61774;61775;61776 | chr2:178556986;178556985;178556984 | chr2:179421713;179421712;179421711 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs1701757178  |
None | 0.543 | N | 0.188 | 0.122 | 0.441324992753 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs1701757178 |
None | 0.543 | N | 0.188 | 0.122 | 0.441324992753 | gnomAD-4.0.0 | 6.57203E-06 | None | None | None | None | I | None | 0 | 6.55308E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | None | None | 0.948 | N | 0.313 | 0.17 | 0.41921206133 | gnomAD-4.0.0 | 1.59132E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85799E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.7074 | likely_pathogenic | 0.6017 | pathogenic | -1.567 | Destabilizing | 0.994 | D | 0.387 | neutral | N | 0.481711132 | None | None | I |
| V/C | 0.8989 | likely_pathogenic | 0.8732 | pathogenic | -1.251 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | I |
| V/D | 0.9445 | likely_pathogenic | 0.9057 | pathogenic | -1.366 | Destabilizing | 0.999 | D | 0.706 | prob.neutral | N | 0.490407638 | None | None | I |
| V/E | 0.886 | likely_pathogenic | 0.8315 | pathogenic | -1.196 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | I |
| V/F | 0.6899 | likely_pathogenic | 0.5768 | pathogenic | -0.922 | Destabilizing | 0.998 | D | 0.669 | neutral | N | 0.49575369 | None | None | I |
| V/G | 0.8295 | likely_pathogenic | 0.7456 | pathogenic | -2.061 | Highly Destabilizing | 0.999 | D | 0.7 | prob.neutral | N | 0.517884156 | None | None | I |
| V/H | 0.9592 | likely_pathogenic | 0.9371 | pathogenic | -1.763 | Destabilizing | 1.0 | D | 0.674 | neutral | None | None | None | None | I |
| V/I | 0.0819 | likely_benign | 0.0794 | benign | -0.233 | Destabilizing | 0.543 | D | 0.188 | neutral | N | 0.467226049 | None | None | I |
| V/K | 0.9125 | likely_pathogenic | 0.8699 | pathogenic | -1.032 | Destabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | I |
| V/L | 0.496 | ambiguous | 0.4005 | ambiguous | -0.233 | Destabilizing | 0.948 | D | 0.313 | neutral | N | 0.508976671 | None | None | I |
| V/M | 0.4249 | ambiguous | 0.3346 | benign | -0.408 | Destabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | I |
| V/N | 0.8373 | likely_pathogenic | 0.7705 | pathogenic | -1.173 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | I |
| V/P | 0.964 | likely_pathogenic | 0.9383 | pathogenic | -0.646 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
| V/Q | 0.881 | likely_pathogenic | 0.8318 | pathogenic | -1.063 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
| V/R | 0.8947 | likely_pathogenic | 0.8419 | pathogenic | -0.952 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | I |
| V/S | 0.8095 | likely_pathogenic | 0.7308 | pathogenic | -1.894 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | I |
| V/T | 0.6601 | likely_pathogenic | 0.583 | pathogenic | -1.573 | Destabilizing | 0.996 | D | 0.544 | neutral | None | None | None | None | I |
| V/W | 0.9903 | likely_pathogenic | 0.9807 | pathogenic | -1.297 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| V/Y | 0.9456 | likely_pathogenic | 0.9135 | pathogenic | -0.885 | Destabilizing | 1.0 | D | 0.68 | 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.