Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17745 | 53458;53459;53460 | chr2:178607455;178607454;178607453 | chr2:179472182;179472181;179472180 |
| N2AB | 16104 | 48535;48536;48537 | chr2:178607455;178607454;178607453 | chr2:179472182;179472181;179472180 |
| N2A | 15177 | 45754;45755;45756 | chr2:178607455;178607454;178607453 | chr2:179472182;179472181;179472180 |
| N2B | 8680 | 26263;26264;26265 | chr2:178607455;178607454;178607453 | chr2:179472182;179472181;179472180 |
| Novex-1 | 8805 | 26638;26639;26640 | chr2:178607455;178607454;178607453 | chr2:179472182;179472181;179472180 |
| Novex-2 | 8872 | 26839;26840;26841 | chr2:178607455;178607454;178607453 | chr2:179472182;179472181;179472180 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs879245504  |
None | 0.988 | N | 0.669 | 0.46 | None | gnomAD-4.0.0 | 1.36887E-06 | None | None | None | None | N | None | 2.99097E-05 | 0 | None | 0 | 2.5227E-05 | None | 0 | 0 | 0 | 0 | 0 |
| T/K | rs879245504 |
-0.418 | 0.852 | D | 0.6 | 0.435 | 0.542053899377 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/K | rs879245504 |
-0.418 | 0.852 | D | 0.6 | 0.435 | 0.542053899377 | gnomAD-4.0.0 | 6.84435E-07 | None | None | None | None | N | None | 0 | 2.23694E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1556 | likely_benign | 0.1214 | benign | -0.932 | Destabilizing | 0.704 | D | 0.475 | neutral | N | 0.501697124 | None | None | N |
| T/C | 0.613 | likely_pathogenic | 0.5099 | ambiguous | -0.638 | Destabilizing | 0.999 | D | 0.649 | neutral | None | None | None | None | N |
| T/D | 0.7986 | likely_pathogenic | 0.7142 | pathogenic | -0.258 | Destabilizing | 0.939 | D | 0.588 | neutral | None | None | None | None | N |
| T/E | 0.4691 | ambiguous | 0.3766 | ambiguous | -0.203 | Destabilizing | 0.884 | D | 0.579 | neutral | None | None | None | None | N |
| T/F | 0.5237 | ambiguous | 0.397 | ambiguous | -0.879 | Destabilizing | 0.997 | D | 0.745 | deleterious | None | None | None | None | N |
| T/G | 0.5928 | likely_pathogenic | 0.4791 | ambiguous | -1.238 | Destabilizing | 0.939 | D | 0.621 | neutral | None | None | None | None | N |
| T/H | 0.4093 | ambiguous | 0.313 | benign | -1.5 | Destabilizing | 0.998 | D | 0.721 | prob.delet. | None | None | None | None | N |
| T/I | 0.3275 | likely_benign | 0.246 | benign | -0.192 | Destabilizing | 0.988 | D | 0.669 | neutral | N | 0.51780209 | None | None | N |
| T/K | 0.2955 | likely_benign | 0.221 | benign | -0.601 | Destabilizing | 0.852 | D | 0.6 | neutral | D | 0.530459169 | None | None | N |
| T/L | 0.2071 | likely_benign | 0.1634 | benign | -0.192 | Destabilizing | 0.939 | D | 0.599 | neutral | None | None | None | None | N |
| T/M | 0.1253 | likely_benign | 0.1099 | benign | -0.02 | Destabilizing | 0.997 | D | 0.673 | neutral | None | None | None | None | N |
| T/N | 0.3301 | likely_benign | 0.2516 | benign | -0.711 | Destabilizing | 0.939 | D | 0.577 | neutral | None | None | None | None | N |
| T/P | 0.8772 | likely_pathogenic | 0.8323 | pathogenic | -0.406 | Destabilizing | 0.988 | D | 0.66 | neutral | D | 0.541236997 | None | None | N |
| T/Q | 0.312 | likely_benign | 0.2469 | benign | -0.788 | Destabilizing | 0.579 | D | 0.386 | neutral | None | None | None | None | N |
| T/R | 0.2747 | likely_benign | 0.1926 | benign | -0.525 | Destabilizing | 0.976 | D | 0.649 | neutral | D | 0.528344371 | None | None | N |
| T/S | 0.2168 | likely_benign | 0.169 | benign | -1.039 | Destabilizing | 0.159 | N | 0.247 | neutral | N | 0.520418321 | None | None | N |
| T/V | 0.241 | likely_benign | 0.1913 | benign | -0.406 | Destabilizing | 0.969 | D | 0.561 | neutral | None | None | None | None | N |
| T/W | 0.8249 | likely_pathogenic | 0.7357 | pathogenic | -0.816 | Destabilizing | 0.999 | D | 0.729 | prob.delet. | None | None | None | None | N |
| T/Y | 0.5143 | ambiguous | 0.3998 | ambiguous | -0.551 | Destabilizing | 0.997 | D | 0.746 | deleterious | 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.