Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13813 | 41662;41663;41664 | chr2:178636134;178636133;178636132 | chr2:179500861;179500860;179500859 |
| N2AB | 12172 | 36739;36740;36741 | chr2:178636134;178636133;178636132 | chr2:179500861;179500860;179500859 |
| N2A | 11245 | 33958;33959;33960 | chr2:178636134;178636133;178636132 | chr2:179500861;179500860;179500859 |
| N2B | 4748 | 14467;14468;14469 | chr2:178636134;178636133;178636132 | chr2:179500861;179500860;179500859 |
| Novex-1 | 4873 | 14842;14843;14844 | chr2:178636134;178636133;178636132 | chr2:179500861;179500860;179500859 |
| Novex-2 | 4940 | 15043;15044;15045 | chr2:178636134;178636133;178636132 | chr2:179500861;179500860;179500859 |
| 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/K | rs374421638  |
-1.601 | 0.022 | N | 0.189 | 0.102 | None | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| R/K | rs374421638 |
-1.601 | 0.022 | N | 0.189 | 0.102 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| R/K | rs374421638 |
-1.601 | 0.022 | N | 0.189 | 0.102 | None | gnomAD-4.0.0 | 5.57951E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.63026E-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 | 0.9255 | likely_pathogenic | 0.9328 | pathogenic | -1.563 | Destabilizing | 0.525 | D | 0.535 | neutral | None | None | None | None | N |
| R/C | 0.4263 | ambiguous | 0.4544 | ambiguous | -1.652 | Destabilizing | 0.998 | D | 0.589 | neutral | None | None | None | None | N |
| R/D | 0.9858 | likely_pathogenic | 0.9874 | pathogenic | -0.473 | Destabilizing | 0.842 | D | 0.583 | neutral | None | None | None | None | N |
| R/E | 0.7474 | likely_pathogenic | 0.771 | pathogenic | -0.347 | Destabilizing | 0.688 | D | 0.511 | neutral | None | None | None | None | N |
| R/F | 0.8762 | likely_pathogenic | 0.8984 | pathogenic | -1.454 | Destabilizing | 0.974 | D | 0.606 | neutral | None | None | None | None | N |
| R/G | 0.8611 | likely_pathogenic | 0.8731 | pathogenic | -1.854 | Destabilizing | 0.801 | D | 0.566 | neutral | N | 0.326470491 | None | None | N |
| R/H | 0.2538 | likely_benign | 0.2715 | benign | -1.838 | Destabilizing | 0.991 | D | 0.525 | neutral | None | None | None | None | N |
| R/I | 0.7011 | likely_pathogenic | 0.7396 | pathogenic | -0.763 | Destabilizing | 0.949 | D | 0.638 | neutral | None | None | None | None | N |
| R/K | 0.1626 | likely_benign | 0.1739 | benign | -1.492 | Destabilizing | 0.022 | N | 0.189 | neutral | N | 0.338070382 | None | None | N |
| R/L | 0.5947 | likely_pathogenic | 0.6381 | pathogenic | -0.763 | Destabilizing | 0.728 | D | 0.572 | neutral | None | None | None | None | N |
| R/M | 0.6317 | likely_pathogenic | 0.6703 | pathogenic | -0.977 | Destabilizing | 0.989 | D | 0.567 | neutral | N | 0.347469257 | None | None | N |
| R/N | 0.945 | likely_pathogenic | 0.9501 | pathogenic | -0.915 | Destabilizing | 0.842 | D | 0.484 | neutral | None | None | None | None | N |
| R/P | 0.9982 | likely_pathogenic | 0.9983 | pathogenic | -1.013 | Destabilizing | 0.974 | D | 0.615 | neutral | None | None | None | None | N |
| R/Q | 0.2156 | likely_benign | 0.231 | benign | -1.17 | Destabilizing | 0.842 | D | 0.517 | neutral | None | None | None | None | N |
| R/S | 0.9278 | likely_pathogenic | 0.9366 | pathogenic | -1.902 | Destabilizing | 0.454 | N | 0.565 | neutral | N | 0.348700506 | None | None | N |
| R/T | 0.7257 | likely_pathogenic | 0.7644 | pathogenic | -1.594 | Destabilizing | 0.051 | N | 0.332 | neutral | N | 0.340511086 | None | None | N |
| R/V | 0.779 | likely_pathogenic | 0.8099 | pathogenic | -1.013 | Destabilizing | 0.728 | D | 0.578 | neutral | None | None | None | None | N |
| R/W | 0.4782 | ambiguous | 0.5217 | ambiguous | -0.958 | Destabilizing | 0.997 | D | 0.589 | neutral | N | 0.346236484 | None | None | N |
| R/Y | 0.726 | likely_pathogenic | 0.7701 | pathogenic | -0.705 | Destabilizing | 0.991 | D | 0.616 | 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.