Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26537 | 79834;79835;79836 | chr2:178566523;178566522;178566521 | chr2:179431250;179431249;179431248 |
| N2AB | 24896 | 74911;74912;74913 | chr2:178566523;178566522;178566521 | chr2:179431250;179431249;179431248 |
| N2A | 23969 | 72130;72131;72132 | chr2:178566523;178566522;178566521 | chr2:179431250;179431249;179431248 |
| N2B | 17472 | 52639;52640;52641 | chr2:178566523;178566522;178566521 | chr2:179431250;179431249;179431248 |
| Novex-1 | 17597 | 53014;53015;53016 | chr2:178566523;178566522;178566521 | chr2:179431250;179431249;179431248 |
| Novex-2 | 17664 | 53215;53216;53217 | chr2:178566523;178566522;178566521 | chr2:179431250;179431249;179431248 |
| 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/D | rs745936423  |
-1.439 | 0.873 | N | 0.579 | 0.228 | 0.59354303687 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| V/D | rs745936423 |
-1.439 | 0.873 | N | 0.579 | 0.228 | 0.59354303687 | gnomAD-4.0.0 | 1.36868E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79904E-06 | 0 | 0 |
| V/L | rs1019110358 |
0.157 | 0.08 | N | 0.3 | 0.136 | 0.406257615169 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| V/L | rs1019110358 |
0.157 | 0.08 | N | 0.3 | 0.136 | 0.406257615169 | gnomAD-4.0.0 | 2.25836E-05 | None | None | None | None | N | None | 2.989E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.87849E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1532 | likely_benign | 0.1319 | benign | -1.215 | Destabilizing | None | N | 0.217 | neutral | N | 0.465041388 | None | None | N |
| V/C | 0.4908 | ambiguous | 0.4245 | ambiguous | -0.832 | Destabilizing | 0.001 | N | 0.292 | neutral | None | None | None | None | N |
| V/D | 0.6153 | likely_pathogenic | 0.5525 | ambiguous | -1.125 | Destabilizing | 0.873 | D | 0.579 | neutral | N | 0.471255609 | None | None | N |
| V/E | 0.4601 | ambiguous | 0.4316 | ambiguous | -1.012 | Destabilizing | 0.561 | D | 0.519 | neutral | None | None | None | None | N |
| V/F | 0.1964 | likely_benign | 0.2003 | benign | -0.714 | Destabilizing | 0.873 | D | 0.531 | neutral | N | 0.46687429 | None | None | N |
| V/G | 0.3176 | likely_benign | 0.2714 | benign | -1.619 | Destabilizing | 0.166 | N | 0.447 | neutral | N | 0.482611915 | None | None | N |
| V/H | 0.6084 | likely_pathogenic | 0.5845 | pathogenic | -1.166 | Destabilizing | 0.991 | D | 0.569 | neutral | None | None | None | None | N |
| V/I | 0.0802 | likely_benign | 0.082 | benign | -0.17 | Destabilizing | 0.285 | N | 0.4 | neutral | N | 0.48428051 | None | None | N |
| V/K | 0.4679 | ambiguous | 0.4431 | ambiguous | -1.013 | Destabilizing | 0.561 | D | 0.517 | neutral | None | None | None | None | N |
| V/L | 0.214 | likely_benign | 0.2118 | benign | -0.17 | Destabilizing | 0.08 | N | 0.3 | neutral | N | 0.50827209 | None | None | N |
| V/M | 0.1785 | likely_benign | 0.1707 | benign | -0.24 | Destabilizing | 0.965 | D | 0.511 | neutral | None | None | None | None | N |
| V/N | 0.4533 | ambiguous | 0.3882 | ambiguous | -1.14 | Destabilizing | 0.901 | D | 0.567 | neutral | None | None | None | None | N |
| V/P | 0.7014 | likely_pathogenic | 0.6443 | pathogenic | -0.485 | Destabilizing | 0.901 | D | 0.571 | neutral | None | None | None | None | N |
| V/Q | 0.4236 | ambiguous | 0.3959 | ambiguous | -1.095 | Destabilizing | 0.901 | D | 0.551 | neutral | None | None | None | None | N |
| V/R | 0.4204 | ambiguous | 0.3989 | ambiguous | -0.758 | Destabilizing | 0.901 | D | 0.579 | neutral | None | None | None | None | N |
| V/S | 0.2636 | likely_benign | 0.223 | benign | -1.698 | Destabilizing | 0.209 | N | 0.414 | neutral | None | None | None | None | N |
| V/T | 0.2235 | likely_benign | 0.1979 | benign | -1.448 | Destabilizing | 0.345 | N | 0.348 | neutral | None | None | None | None | N |
| V/W | 0.8456 | likely_pathogenic | 0.8414 | pathogenic | -1.064 | Destabilizing | 0.991 | D | 0.603 | neutral | None | None | None | None | N |
| V/Y | 0.5561 | ambiguous | 0.5389 | ambiguous | -0.648 | Destabilizing | 0.965 | D | 0.523 | neutral | 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.