Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26655 | 80188;80189;80190 | chr2:178566169;178566168;178566167 | chr2:179430896;179430895;179430894 |
| N2AB | 25014 | 75265;75266;75267 | chr2:178566169;178566168;178566167 | chr2:179430896;179430895;179430894 |
| N2A | 24087 | 72484;72485;72486 | chr2:178566169;178566168;178566167 | chr2:179430896;179430895;179430894 |
| N2B | 17590 | 52993;52994;52995 | chr2:178566169;178566168;178566167 | chr2:179430896;179430895;179430894 |
| Novex-1 | 17715 | 53368;53369;53370 | chr2:178566169;178566168;178566167 | chr2:179430896;179430895;179430894 |
| Novex-2 | 17782 | 53569;53570;53571 | chr2:178566169;178566168;178566167 | chr2:179430896;179430895;179430894 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/I | None | None | 0.97 | N | 0.523 | 0.335 | 0.353974658523 | gnomAD-4.0.0 | 6.84258E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99533E-07 | 0 | 0 |
| R/K | rs1186804740  |
0.353 | 0.025 | N | 0.241 | 0.09 | 0.218112801441 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| R/K | rs1186804740 |
0.353 | 0.025 | N | 0.241 | 0.09 | 0.218112801441 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/K | rs1186804740 |
0.353 | 0.025 | N | 0.241 | 0.09 | 0.218112801441 | gnomAD-4.0.0 | 1.23948E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69533E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9751 | likely_pathogenic | 0.9706 | pathogenic | -0.017 | Destabilizing | 0.86 | D | 0.511 | neutral | None | None | None | None | N |
| R/C | 0.7777 | likely_pathogenic | 0.7546 | pathogenic | -0.111 | Destabilizing | 0.998 | D | 0.536 | neutral | None | None | None | None | N |
| R/D | 0.9955 | likely_pathogenic | 0.9942 | pathogenic | -0.174 | Destabilizing | 0.956 | D | 0.469 | neutral | None | None | None | None | N |
| R/E | 0.9554 | likely_pathogenic | 0.9467 | pathogenic | -0.122 | Destabilizing | 0.86 | D | 0.478 | neutral | None | None | None | None | N |
| R/F | 0.986 | likely_pathogenic | 0.9776 | pathogenic | -0.267 | Destabilizing | 0.978 | D | 0.523 | neutral | None | None | None | None | N |
| R/G | 0.9526 | likely_pathogenic | 0.942 | pathogenic | -0.196 | Destabilizing | 0.822 | D | 0.526 | neutral | N | 0.507246629 | None | None | N |
| R/H | 0.5784 | likely_pathogenic | 0.5233 | ambiguous | -0.695 | Destabilizing | 0.043 | N | 0.33 | neutral | None | None | None | None | N |
| R/I | 0.9275 | likely_pathogenic | 0.9015 | pathogenic | 0.416 | Stabilizing | 0.97 | D | 0.523 | neutral | N | 0.473885274 | None | None | N |
| R/K | 0.3979 | ambiguous | 0.379 | ambiguous | -0.095 | Destabilizing | 0.025 | N | 0.241 | neutral | N | 0.494188072 | None | None | N |
| R/L | 0.9214 | likely_pathogenic | 0.8964 | pathogenic | 0.416 | Stabilizing | 0.86 | D | 0.499 | neutral | None | None | None | None | N |
| R/M | 0.9502 | likely_pathogenic | 0.931 | pathogenic | 0.051 | Stabilizing | 0.998 | D | 0.515 | neutral | None | None | None | None | N |
| R/N | 0.9886 | likely_pathogenic | 0.9855 | pathogenic | 0.157 | Stabilizing | 0.86 | D | 0.491 | neutral | None | None | None | None | N |
| R/P | 0.9842 | likely_pathogenic | 0.9817 | pathogenic | 0.291 | Stabilizing | 0.993 | D | 0.523 | neutral | None | None | None | None | N |
| R/Q | 0.5357 | ambiguous | 0.4941 | ambiguous | 0.043 | Stabilizing | 0.86 | D | 0.503 | neutral | None | None | None | None | N |
| R/S | 0.9859 | likely_pathogenic | 0.9821 | pathogenic | -0.155 | Destabilizing | 0.822 | D | 0.544 | neutral | N | 0.483101986 | None | None | N |
| R/T | 0.9727 | likely_pathogenic | 0.9604 | pathogenic | 0.02 | Stabilizing | 0.904 | D | 0.507 | neutral | N | 0.485406164 | None | None | N |
| R/V | 0.9582 | likely_pathogenic | 0.9453 | pathogenic | 0.291 | Stabilizing | 0.978 | D | 0.513 | neutral | None | None | None | None | N |
| R/W | 0.7925 | likely_pathogenic | 0.7261 | pathogenic | -0.347 | Destabilizing | 0.998 | D | 0.553 | neutral | None | None | None | None | N |
| R/Y | 0.9521 | likely_pathogenic | 0.9355 | pathogenic | 0.058 | Stabilizing | 0.915 | D | 0.52 | 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.