Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4657 | 14194;14195;14196 | chr2:178739264;178739263;178739262 | chr2:179603991;179603990;179603989 |
| N2AB | 4340 | 13243;13244;13245 | chr2:178739264;178739263;178739262 | chr2:179603991;179603990;179603989 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 4294 | 13105;13106;13107 | chr2:178739264;178739263;178739262 | chr2:179603991;179603990;179603989 |
| Novex-1 | 4419 | 13480;13481;13482 | chr2:178739264;178739263;178739262 | chr2:179603991;179603990;179603989 |
| Novex-2 | 4486 | 13681;13682;13683 | chr2:178739264;178739263;178739262 | chr2:179603991;179603990;179603989 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/H | rs200204761  |
-1.102 | 0.602 | D | 0.474 | 0.22 | None | gnomAD-2.1.1 | 2.47713E-03 | None | None | None | None | N | None | 1.6544E-04 | 3.12767E-04 | None | 1.07737E-03 | 0 | None | 1.78018E-02 | None | 1.21007E-04 | 8.2393E-04 | 2.26372E-03 |
| N/H | rs200204761 |
-1.102 | 0.602 | D | 0.474 | 0.22 | None | gnomAD-3.1.2 | 9.00025E-04 | None | None | None | None | N | None | 9.65E-05 | 3.92722E-04 | 2.19298E-03 | 2.88184E-04 | 0 | None | 4.70278E-04 | 0 | 6.46735E-04 | 1.55151E-02 | 0 |
| N/H | rs200204761 |
-1.102 | 0.602 | D | 0.474 | 0.22 | None | 1000 genomes | 2.99521E-03 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1.53E-02 | None |
| N/H | rs200204761 |
-1.102 | 0.602 | D | 0.474 | 0.22 | None | gnomAD-4.0.0 | 1.52586E-03 | None | None | None | None | N | None | 1.06695E-04 | 3.50631E-04 | None | 8.4786E-04 | 0 | None | 9.38879E-05 | 5.291E-03 | 6.24379E-04 | 1.69715E-02 | 1.38028E-03 |
| N/K | None | None | None | N | 0.094 | 0.144 | None | gnomAD-4.0.0 | 1.60093E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8806E-06 | 0 | 0 |
| N/T | None | None | 0.081 | N | 0.295 | 0.249 | None | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.3165 | likely_benign | 0.356 | ambiguous | -0.828 | Destabilizing | 0.055 | N | 0.49 | neutral | None | None | None | None | N |
| N/C | 0.4052 | ambiguous | 0.4323 | ambiguous | 0.128 | Stabilizing | 0.958 | D | 0.568 | neutral | None | None | None | None | N |
| N/D | 0.1002 | likely_benign | 0.1035 | benign | -0.469 | Destabilizing | None | N | 0.121 | neutral | N | 0.460837066 | None | None | N |
| N/E | 0.3076 | likely_benign | 0.3415 | ambiguous | -0.413 | Destabilizing | 0.025 | N | 0.243 | neutral | None | None | None | None | N |
| N/F | 0.558 | ambiguous | 0.5995 | pathogenic | -0.754 | Destabilizing | 0.859 | D | 0.597 | neutral | None | None | None | None | N |
| N/G | 0.2967 | likely_benign | 0.3216 | benign | -1.132 | Destabilizing | 0.104 | N | 0.323 | neutral | None | None | None | None | N |
| N/H | 0.1325 | likely_benign | 0.1343 | benign | -0.993 | Destabilizing | 0.602 | D | 0.474 | neutral | D | 0.558690168 | None | None | N |
| N/I | 0.347 | ambiguous | 0.4055 | ambiguous | -0.073 | Destabilizing | 0.602 | D | 0.589 | neutral | D | 0.615111744 | None | None | N |
| N/K | 0.2583 | likely_benign | 0.2916 | benign | -0.241 | Destabilizing | None | N | 0.094 | neutral | N | 0.503108516 | None | None | N |
| N/L | 0.3374 | likely_benign | 0.3754 | ambiguous | -0.073 | Destabilizing | 0.22 | N | 0.571 | neutral | None | None | None | None | N |
| N/M | 0.3796 | ambiguous | 0.4096 | ambiguous | 0.507 | Stabilizing | 0.958 | D | 0.542 | neutral | None | None | None | None | N |
| N/P | 0.7821 | likely_pathogenic | 0.8305 | pathogenic | -0.295 | Destabilizing | 0.364 | N | 0.539 | neutral | None | None | None | None | N |
| N/Q | 0.3256 | likely_benign | 0.3521 | ambiguous | -0.85 | Destabilizing | 0.124 | N | 0.38 | neutral | None | None | None | None | N |
| N/R | 0.3425 | ambiguous | 0.3843 | ambiguous | -0.227 | Destabilizing | 0.124 | N | 0.323 | neutral | None | None | None | None | N |
| N/S | 0.133 | likely_benign | 0.1434 | benign | -0.762 | Destabilizing | 0.042 | N | 0.345 | neutral | N | 0.507370455 | None | None | N |
| N/T | 0.1976 | likely_benign | 0.2186 | benign | -0.521 | Destabilizing | 0.081 | N | 0.295 | neutral | N | 0.511072364 | None | None | N |
| N/V | 0.3707 | ambiguous | 0.4284 | ambiguous | -0.295 | Destabilizing | 0.22 | N | 0.568 | neutral | None | None | None | None | N |
| N/W | 0.778 | likely_pathogenic | 0.8044 | pathogenic | -0.542 | Destabilizing | 0.958 | D | 0.625 | neutral | None | None | None | None | N |
| N/Y | 0.1705 | likely_benign | 0.1914 | benign | -0.342 | Destabilizing | 0.822 | D | 0.572 | neutral | D | 0.653939605 | 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.