Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15001 | 45226;45227;45228 | chr2:178621921;178621920;178621919 | chr2:179486648;179486647;179486646 |
| N2AB | 13360 | 40303;40304;40305 | chr2:178621921;178621920;178621919 | chr2:179486648;179486647;179486646 |
| N2A | 12433 | 37522;37523;37524 | chr2:178621921;178621920;178621919 | chr2:179486648;179486647;179486646 |
| N2B | 5936 | 18031;18032;18033 | chr2:178621921;178621920;178621919 | chr2:179486648;179486647;179486646 |
| Novex-1 | 6061 | 18406;18407;18408 | chr2:178621921;178621920;178621919 | chr2:179486648;179486647;179486646 |
| Novex-2 | 6128 | 18607;18608;18609 | chr2:178621921;178621920;178621919 | chr2:179486648;179486647;179486646 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/H | rs373109469  |
-0.964 | 0.004 | N | 0.117 | 0.156 | None | gnomAD-2.1.1 | 4.44E-05 | None | None | None | None | N | None | 0 | 8.75E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 6.24E-05 | 0 |
| N/H | rs373109469 |
-0.964 | 0.004 | N | 0.117 | 0.156 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06782E-04 | 0 |
| N/H | rs373109469 |
-0.964 | 0.004 | N | 0.117 | 0.156 | None | gnomAD-4.0.0 | 3.41181E-05 | None | None | None | None | N | None | 0 | 6.68919E-05 | None | 0 | 0 | None | 0 | 0 | 3.22315E-05 | 6.59196E-05 | 1.12244E-04 |
| N/K | None | None | 0.379 | N | 0.288 | 0.15 | 0.17258766438 | gnomAD-4.0.0 | 1.36982E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.73913E-04 | 9.00053E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.3573 | ambiguous | 0.4139 | ambiguous | -0.602 | Destabilizing | 0.25 | N | 0.361 | neutral | None | None | None | None | N |
| N/C | 0.4802 | ambiguous | 0.5461 | ambiguous | 0.109 | Stabilizing | 0.992 | D | 0.452 | neutral | None | None | None | None | N |
| N/D | 0.2891 | likely_benign | 0.2817 | benign | -1.076 | Destabilizing | 0.549 | D | 0.341 | neutral | N | 0.489060695 | None | None | N |
| N/E | 0.5408 | ambiguous | 0.5617 | ambiguous | -0.959 | Destabilizing | 0.617 | D | 0.29 | neutral | None | None | None | None | N |
| N/F | 0.7492 | likely_pathogenic | 0.8049 | pathogenic | -0.344 | Destabilizing | 0.92 | D | 0.474 | neutral | None | None | None | None | N |
| N/G | 0.2801 | likely_benign | 0.3226 | benign | -0.964 | Destabilizing | 0.25 | N | 0.284 | neutral | None | None | None | None | N |
| N/H | 0.108 | likely_benign | 0.1167 | benign | -0.86 | Destabilizing | 0.004 | N | 0.117 | neutral | N | 0.425144919 | None | None | N |
| N/I | 0.5218 | ambiguous | 0.5919 | pathogenic | 0.322 | Stabilizing | 0.896 | D | 0.469 | neutral | N | 0.507472304 | None | None | N |
| N/K | 0.4072 | ambiguous | 0.424 | ambiguous | -0.305 | Destabilizing | 0.379 | N | 0.288 | neutral | N | 0.482248862 | None | None | N |
| N/L | 0.403 | ambiguous | 0.4646 | ambiguous | 0.322 | Stabilizing | 0.617 | D | 0.433 | neutral | None | None | None | None | N |
| N/M | 0.5926 | likely_pathogenic | 0.6624 | pathogenic | 0.82 | Stabilizing | 0.992 | D | 0.43 | neutral | None | None | None | None | N |
| N/P | 0.4814 | ambiguous | 0.4941 | ambiguous | 0.045 | Stabilizing | 0.92 | D | 0.435 | neutral | None | None | None | None | N |
| N/Q | 0.3703 | ambiguous | 0.412 | ambiguous | -0.943 | Destabilizing | 0.85 | D | 0.349 | neutral | None | None | None | None | N |
| N/R | 0.4016 | ambiguous | 0.4117 | ambiguous | -0.421 | Destabilizing | 0.617 | D | 0.334 | neutral | None | None | None | None | N |
| N/S | 0.0785 | likely_benign | 0.085 | benign | -0.916 | Destabilizing | 0.007 | N | 0.086 | neutral | N | 0.434925897 | None | None | N |
| N/T | 0.1938 | likely_benign | 0.2249 | benign | -0.617 | Destabilizing | 0.379 | N | 0.291 | neutral | N | 0.495865794 | None | None | N |
| N/V | 0.5114 | ambiguous | 0.5913 | pathogenic | 0.045 | Stabilizing | 0.85 | D | 0.445 | neutral | None | None | None | None | N |
| N/W | 0.8109 | likely_pathogenic | 0.84 | pathogenic | -0.216 | Destabilizing | 0.992 | D | 0.54 | neutral | None | None | None | None | N |
| N/Y | 0.2579 | likely_benign | 0.2949 | benign | 0.058 | Stabilizing | 0.81 | D | 0.436 | neutral | N | 0.507580693 | 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.