Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31877 | 95854;95855;95856 | chr2:178545481;178545480;178545479 | chr2:179410208;179410207;179410206 |
| N2AB | 30236 | 90931;90932;90933 | chr2:178545481;178545480;178545479 | chr2:179410208;179410207;179410206 |
| N2A | 29309 | 88150;88151;88152 | chr2:178545481;178545480;178545479 | chr2:179410208;179410207;179410206 |
| N2B | 22812 | 68659;68660;68661 | chr2:178545481;178545480;178545479 | chr2:179410208;179410207;179410206 |
| Novex-1 | 22937 | 69034;69035;69036 | chr2:178545481;178545480;178545479 | chr2:179410208;179410207;179410206 |
| Novex-2 | 23004 | 69235;69236;69237 | chr2:178545481;178545480;178545479 | chr2:179410208;179410207;179410206 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/Y | rs1335546534  |
-1.549 | 0.921 | N | 0.562 | 0.3 | 0.670770561155 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14705E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| C/Y | rs1335546534 |
-1.549 | 0.921 | N | 0.562 | 0.3 | 0.670770561155 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| C/Y | rs1335546534 |
-1.549 | 0.921 | N | 0.562 | 0.3 | 0.670770561155 | gnomAD-4.0.0 | 6.57142E-06 | None | None | None | None | N | None | 2.41231E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.2706 | likely_benign | 0.2738 | benign | -1.962 | Destabilizing | 0.061 | N | 0.267 | neutral | None | None | None | None | N |
| C/D | 0.6194 | likely_pathogenic | 0.6467 | pathogenic | -0.413 | Destabilizing | 0.418 | N | 0.545 | neutral | None | None | None | None | N |
| C/E | 0.7627 | likely_pathogenic | 0.7707 | pathogenic | -0.331 | Destabilizing | 0.418 | N | 0.538 | neutral | None | None | None | None | N |
| C/F | 0.224 | likely_benign | 0.2158 | benign | -1.375 | Destabilizing | 0.794 | D | 0.553 | neutral | N | 0.490254837 | None | None | N |
| C/G | 0.1526 | likely_benign | 0.1439 | benign | -2.251 | Highly Destabilizing | 0.001 | N | 0.229 | neutral | N | 0.450755087 | None | None | N |
| C/H | 0.3851 | ambiguous | 0.3595 | ambiguous | -2.099 | Highly Destabilizing | 0.836 | D | 0.574 | neutral | None | None | None | None | N |
| C/I | 0.4545 | ambiguous | 0.466 | ambiguous | -1.219 | Destabilizing | 0.593 | D | 0.521 | neutral | None | None | None | None | N |
| C/K | 0.7331 | likely_pathogenic | 0.7224 | pathogenic | -1.034 | Destabilizing | 0.264 | N | 0.545 | neutral | None | None | None | None | N |
| C/L | 0.4142 | ambiguous | 0.4324 | ambiguous | -1.219 | Destabilizing | 0.228 | N | 0.481 | neutral | None | None | None | None | N |
| C/M | 0.4582 | ambiguous | 0.4843 | ambiguous | -0.203 | Destabilizing | 0.94 | D | 0.514 | neutral | None | None | None | None | N |
| C/N | 0.2167 | likely_benign | 0.243 | benign | -0.939 | Destabilizing | 0.264 | N | 0.545 | neutral | None | None | None | None | N |
| C/P | 0.9756 | likely_pathogenic | 0.9764 | pathogenic | -1.442 | Destabilizing | 0.836 | D | 0.605 | neutral | None | None | None | None | N |
| C/Q | 0.5154 | ambiguous | 0.4858 | ambiguous | -0.915 | Destabilizing | 0.716 | D | 0.591 | neutral | None | None | None | None | N |
| C/R | 0.4552 | ambiguous | 0.4195 | ambiguous | -0.758 | Destabilizing | 0.655 | D | 0.599 | neutral | N | 0.419680031 | None | None | N |
| C/S | 0.1394 | likely_benign | 0.1443 | benign | -1.528 | Destabilizing | 0.001 | N | 0.201 | neutral | N | 0.391744069 | None | None | N |
| C/T | 0.2781 | likely_benign | 0.2886 | benign | -1.268 | Destabilizing | 0.129 | N | 0.465 | neutral | None | None | None | None | N |
| C/V | 0.3613 | ambiguous | 0.3753 | ambiguous | -1.442 | Destabilizing | 0.418 | N | 0.48 | neutral | None | None | None | None | N |
| C/W | 0.5275 | ambiguous | 0.4725 | ambiguous | -1.268 | Destabilizing | 0.978 | D | 0.525 | neutral | N | 0.482616789 | None | None | N |
| C/Y | 0.2832 | likely_benign | 0.2659 | benign | -1.308 | Destabilizing | 0.921 | D | 0.562 | neutral | N | 0.508840598 | 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.