Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18021 | 54286;54287;54288 | chr2:178605116;178605115;178605114 | chr2:179469843;179469842;179469841 |
| N2AB | 16380 | 49363;49364;49365 | chr2:178605116;178605115;178605114 | chr2:179469843;179469842;179469841 |
| N2A | 15453 | 46582;46583;46584 | chr2:178605116;178605115;178605114 | chr2:179469843;179469842;179469841 |
| N2B | 8956 | 27091;27092;27093 | chr2:178605116;178605115;178605114 | chr2:179469843;179469842;179469841 |
| Novex-1 | 9081 | 27466;27467;27468 | chr2:178605116;178605115;178605114 | chr2:179469843;179469842;179469841 |
| Novex-2 | 9148 | 27667;27668;27669 | chr2:178605116;178605115;178605114 | chr2:179469843;179469842;179469841 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1039563833  |
-0.292 | 0.454 | N | 0.29 | 0.088 | 0.31291088546 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs1039563833 |
-0.292 | 0.454 | N | 0.29 | 0.088 | 0.31291088546 | gnomAD-4.0.0 | 6.84605E-07 | None | None | None | None | I | None | 2.99294E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/E | None | None | 0.934 | N | 0.36 | 0.253 | 0.345175991111 | gnomAD-4.0.0 | 6.84605E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65793E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1829 | likely_benign | 0.1796 | benign | -0.644 | Destabilizing | 0.454 | N | 0.29 | neutral | N | 0.424018698 | None | None | I |
| V/C | 0.7035 | likely_pathogenic | 0.7058 | pathogenic | -0.62 | Destabilizing | 0.998 | D | 0.283 | neutral | None | None | None | None | I |
| V/D | 0.3123 | likely_benign | 0.3057 | benign | -0.53 | Destabilizing | 0.949 | D | 0.406 | neutral | None | None | None | None | I |
| V/E | 0.2371 | likely_benign | 0.2457 | benign | -0.652 | Destabilizing | 0.934 | D | 0.36 | neutral | N | 0.467038756 | None | None | I |
| V/F | 0.151 | likely_benign | 0.1453 | benign | -0.875 | Destabilizing | 0.974 | D | 0.269 | neutral | None | None | None | None | I |
| V/G | 0.1934 | likely_benign | 0.1789 | benign | -0.786 | Destabilizing | 0.934 | D | 0.395 | neutral | N | 0.44679677 | None | None | I |
| V/H | 0.4519 | ambiguous | 0.4677 | ambiguous | -0.313 | Destabilizing | 0.998 | D | 0.419 | neutral | None | None | None | None | I |
| V/I | 0.0674 | likely_benign | 0.0659 | benign | -0.416 | Destabilizing | 0.022 | N | 0.115 | neutral | N | 0.376054179 | None | None | I |
| V/K | 0.253 | likely_benign | 0.2778 | benign | -0.51 | Destabilizing | 0.949 | D | 0.363 | neutral | None | None | None | None | I |
| V/L | 0.1461 | likely_benign | 0.1448 | benign | -0.416 | Destabilizing | 0.454 | N | 0.242 | neutral | N | 0.419170238 | None | None | I |
| V/M | 0.1353 | likely_benign | 0.1284 | benign | -0.33 | Destabilizing | 0.974 | D | 0.237 | neutral | None | None | None | None | I |
| V/N | 0.2043 | likely_benign | 0.195 | benign | -0.201 | Destabilizing | 0.949 | D | 0.41 | neutral | None | None | None | None | I |
| V/P | 0.6585 | likely_pathogenic | 0.6544 | pathogenic | -0.457 | Destabilizing | 0.974 | D | 0.371 | neutral | None | None | None | None | I |
| V/Q | 0.2652 | likely_benign | 0.2833 | benign | -0.51 | Destabilizing | 0.974 | D | 0.357 | neutral | None | None | None | None | I |
| V/R | 0.282 | likely_benign | 0.3033 | benign | 0.09 | Stabilizing | 0.974 | D | 0.399 | neutral | None | None | None | None | I |
| V/S | 0.2032 | likely_benign | 0.1941 | benign | -0.567 | Destabilizing | 0.728 | D | 0.381 | neutral | None | None | None | None | I |
| V/T | 0.1534 | likely_benign | 0.1541 | benign | -0.593 | Destabilizing | 0.029 | N | 0.105 | neutral | None | None | None | None | I |
| V/W | 0.7103 | likely_pathogenic | 0.7113 | pathogenic | -0.918 | Destabilizing | 0.998 | D | 0.525 | neutral | None | None | None | None | I |
| V/Y | 0.4385 | ambiguous | 0.4256 | ambiguous | -0.626 | Destabilizing | 0.991 | D | 0.257 | neutral | None | None | None | None | I |
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.