Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14754 | 44485;44486;44487 | chr2:178630262;178630261;178630260 | chr2:179494989;179494988;179494987 |
| N2AB | 13113 | 39562;39563;39564 | chr2:178630262;178630261;178630260 | chr2:179494989;179494988;179494987 |
| N2A | 12186 | 36781;36782;36783 | chr2:178630262;178630261;178630260 | chr2:179494989;179494988;179494987 |
| N2B | 5689 | 17290;17291;17292 | chr2:178630262;178630261;178630260 | chr2:179494989;179494988;179494987 |
| Novex-1 | 5814 | 17665;17666;17667 | chr2:178630262;178630261;178630260 | chr2:179494989;179494988;179494987 |
| Novex-2 | 5881 | 17866;17867;17868 | chr2:178630262;178630261;178630260 | chr2:179494989;179494988;179494987 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/I | rs377344521  |
-0.119 | 0.976 | D | 0.711 | 0.343 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/I | rs377344521 |
-0.119 | 0.976 | D | 0.711 | 0.343 | None | gnomAD-4.0.0 | 1.2399E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69572E-06 | 0 | 0 |
| S/T | rs377344521 |
-0.08 | 0.791 | N | 0.589 | 0.184 | 0.16115917748 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| S/T | rs377344521 |
-0.08 | 0.791 | N | 0.589 | 0.184 | 0.16115917748 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/T | rs377344521 |
-0.08 | 0.791 | N | 0.589 | 0.184 | 0.16115917748 | gnomAD-4.0.0 | 2.4798E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39143E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1061 | likely_benign | 0.1247 | benign | -0.477 | Destabilizing | 0.338 | N | 0.518 | neutral | None | None | None | None | N |
| S/C | 0.1596 | likely_benign | 0.2014 | benign | -0.303 | Destabilizing | 0.993 | D | 0.588 | neutral | D | 0.563894095 | None | None | N |
| S/D | 0.5855 | likely_pathogenic | 0.738 | pathogenic | 0.149 | Stabilizing | 0.008 | N | 0.303 | neutral | None | None | None | None | N |
| S/E | 0.6324 | likely_pathogenic | 0.7671 | pathogenic | 0.058 | Stabilizing | 0.553 | D | 0.578 | neutral | None | None | None | None | N |
| S/F | 0.2751 | likely_benign | 0.3541 | ambiguous | -1.056 | Destabilizing | 0.982 | D | 0.698 | prob.delet. | None | None | None | None | N |
| S/G | 0.1235 | likely_benign | 0.1517 | benign | -0.593 | Destabilizing | 0.006 | N | 0.27 | neutral | N | 0.480295448 | None | None | N |
| S/H | 0.3854 | ambiguous | 0.5143 | ambiguous | -1.15 | Destabilizing | 0.995 | D | 0.593 | neutral | None | None | None | None | N |
| S/I | 0.2262 | likely_benign | 0.2943 | benign | -0.297 | Destabilizing | 0.976 | D | 0.711 | prob.delet. | D | 0.559435028 | None | None | N |
| S/K | 0.6676 | likely_pathogenic | 0.825 | pathogenic | -0.459 | Destabilizing | 0.032 | N | 0.334 | neutral | None | None | None | None | N |
| S/L | 0.1567 | likely_benign | 0.201 | benign | -0.297 | Destabilizing | 0.834 | D | 0.643 | neutral | None | None | None | None | N |
| S/M | 0.252 | likely_benign | 0.2945 | benign | 0.036 | Stabilizing | 0.995 | D | 0.579 | neutral | None | None | None | None | N |
| S/N | 0.1676 | likely_benign | 0.2332 | benign | -0.192 | Destabilizing | 0.651 | D | 0.554 | neutral | N | 0.520077624 | None | None | N |
| S/P | 0.8234 | likely_pathogenic | 0.9099 | pathogenic | -0.328 | Destabilizing | 0.982 | D | 0.617 | neutral | None | None | None | None | N |
| S/Q | 0.5313 | ambiguous | 0.6469 | pathogenic | -0.474 | Destabilizing | 0.897 | D | 0.581 | neutral | None | None | None | None | N |
| S/R | 0.5539 | ambiguous | 0.721 | pathogenic | -0.27 | Destabilizing | 0.766 | D | 0.612 | neutral | N | 0.496678493 | None | None | N |
| S/T | 0.0847 | likely_benign | 0.0992 | benign | -0.318 | Destabilizing | 0.791 | D | 0.589 | neutral | N | 0.4404069 | None | None | N |
| S/V | 0.2231 | likely_benign | 0.2705 | benign | -0.328 | Destabilizing | 0.946 | D | 0.64 | neutral | None | None | None | None | N |
| S/W | 0.4903 | ambiguous | 0.6045 | pathogenic | -1.024 | Destabilizing | 0.995 | D | 0.723 | deleterious | None | None | None | None | N |
| S/Y | 0.2696 | likely_benign | 0.3733 | ambiguous | -0.754 | Destabilizing | 0.982 | D | 0.703 | prob.delet. | 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.