Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18936 | 57031;57032;57033 | chr2:178598904;178598903;178598902 | chr2:179463631;179463630;179463629 |
| N2AB | 17295 | 52108;52109;52110 | chr2:178598904;178598903;178598902 | chr2:179463631;179463630;179463629 |
| N2A | 16368 | 49327;49328;49329 | chr2:178598904;178598903;178598902 | chr2:179463631;179463630;179463629 |
| N2B | 9871 | 29836;29837;29838 | chr2:178598904;178598903;178598902 | chr2:179463631;179463630;179463629 |
| Novex-1 | 9996 | 30211;30212;30213 | chr2:178598904;178598903;178598902 | chr2:179463631;179463630;179463629 |
| Novex-2 | 10063 | 30412;30413;30414 | chr2:178598904;178598903;178598902 | chr2:179463631;179463630;179463629 |
| 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/Q | rs745914315  |
0.206 | 0.999 | N | 0.546 | 0.341 | 0.228597637076 | gnomAD-2.1.1 | 3.58E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.85E-05 | 0 |
| R/Q | rs745914315 |
0.206 | 0.999 | N | 0.546 | 0.341 | 0.228597637076 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/Q | rs745914315 |
0.206 | 0.999 | N | 0.546 | 0.341 | 0.228597637076 | gnomAD-4.0.0 | 2.47986E-05 | None | None | None | None | I | None | 1.33661E-05 | 1.66884E-05 | None | 0 | 4.47247E-05 | None | 0 | 0 | 3.05218E-05 | 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 | 0.8414 | likely_pathogenic | 0.7986 | pathogenic | 0.038 | Stabilizing | 0.91 | D | 0.546 | neutral | None | None | None | None | I |
| R/C | 0.6223 | likely_pathogenic | 0.6309 | pathogenic | -0.27 | Destabilizing | 0.999 | D | 0.591 | neutral | None | None | None | None | I |
| R/D | 0.9231 | likely_pathogenic | 0.9067 | pathogenic | -0.408 | Destabilizing | 0.986 | D | 0.477 | neutral | None | None | None | None | I |
| R/E | 0.8156 | likely_pathogenic | 0.7734 | pathogenic | -0.374 | Destabilizing | 0.976 | D | 0.523 | neutral | None | None | None | None | I |
| R/F | 0.9454 | likely_pathogenic | 0.9196 | pathogenic | -0.3 | Destabilizing | 0.998 | D | 0.557 | neutral | None | None | None | None | I |
| R/G | 0.725 | likely_pathogenic | 0.6612 | pathogenic | -0.082 | Destabilizing | 0.109 | N | 0.438 | neutral | N | 0.48132871 | None | None | I |
| R/H | 0.3249 | likely_benign | 0.2828 | benign | -0.604 | Destabilizing | 0.998 | D | 0.528 | neutral | None | None | None | None | I |
| R/I | 0.8224 | likely_pathogenic | 0.7356 | pathogenic | 0.309 | Stabilizing | 0.998 | D | 0.562 | neutral | None | None | None | None | I |
| R/K | 0.1859 | likely_benign | 0.1632 | benign | -0.208 | Destabilizing | 0.893 | D | 0.541 | neutral | None | None | None | None | I |
| R/L | 0.7615 | likely_pathogenic | 0.7005 | pathogenic | 0.309 | Stabilizing | 0.996 | D | 0.431 | neutral | N | 0.485654307 | None | None | I |
| R/M | 0.8128 | likely_pathogenic | 0.7197 | pathogenic | -0.139 | Destabilizing | 0.999 | D | 0.504 | neutral | None | None | None | None | I |
| R/N | 0.8979 | likely_pathogenic | 0.8653 | pathogenic | -0.145 | Destabilizing | 0.986 | D | 0.517 | neutral | None | None | None | None | I |
| R/P | 0.8394 | likely_pathogenic | 0.8177 | pathogenic | 0.235 | Stabilizing | 0.999 | D | 0.506 | neutral | N | 0.475402815 | None | None | I |
| R/Q | 0.2945 | likely_benign | 0.2675 | benign | -0.159 | Destabilizing | 0.999 | D | 0.546 | neutral | N | 0.48384894 | None | None | I |
| R/S | 0.8761 | likely_pathogenic | 0.8488 | pathogenic | -0.255 | Destabilizing | 0.953 | D | 0.505 | neutral | None | None | None | None | I |
| R/T | 0.7398 | likely_pathogenic | 0.6251 | pathogenic | -0.127 | Destabilizing | 0.993 | D | 0.461 | neutral | None | None | None | None | I |
| R/V | 0.8397 | likely_pathogenic | 0.7778 | pathogenic | 0.235 | Stabilizing | 0.993 | D | 0.561 | neutral | None | None | None | None | I |
| R/W | 0.5952 | likely_pathogenic | 0.5149 | ambiguous | -0.523 | Destabilizing | 0.999 | D | 0.61 | neutral | None | None | None | None | I |
| R/Y | 0.8352 | likely_pathogenic | 0.7869 | pathogenic | -0.128 | Destabilizing | 0.998 | D | 0.519 | 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.