Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33314 | 100165;100166;100167 | chr2:178537169;178537168;178537167 | chr2:179401896;179401895;179401894 |
| N2AB | 31673 | 95242;95243;95244 | chr2:178537169;178537168;178537167 | chr2:179401896;179401895;179401894 |
| N2A | 30746 | 92461;92462;92463 | chr2:178537169;178537168;178537167 | chr2:179401896;179401895;179401894 |
| N2B | 24249 | 72970;72971;72972 | chr2:178537169;178537168;178537167 | chr2:179401896;179401895;179401894 |
| Novex-1 | 24374 | 73345;73346;73347 | chr2:178537169;178537168;178537167 | chr2:179401896;179401895;179401894 |
| Novex-2 | 24441 | 73546;73547;73548 | chr2:178537169;178537168;178537167 | chr2:179401896;179401895;179401894 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | None | None | 0.698 | N | 0.63 | 0.47 | 0.638834684723 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 0 |
| P/S | rs754605294  |
-1.696 | 0.698 | N | 0.553 | 0.265 | None | gnomAD-2.1.1 | 3.58E-05 | None | None | None | None | N | None | 2.06748E-04 | 1.41739E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs754605294 |
-1.696 | 0.698 | N | 0.553 | 0.265 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 1.68943E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs754605294 |
-1.696 | 0.698 | N | 0.553 | 0.265 | None | gnomAD-4.0.0 | 1.17756E-05 | None | None | None | None | N | None | 1.46874E-04 | 1.0006E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.20287E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0966 | likely_benign | 0.088 | benign | -1.738 | Destabilizing | 0.006 | N | 0.287 | neutral | N | 0.509614176 | None | None | N |
| P/C | 0.7221 | likely_pathogenic | 0.7116 | pathogenic | -1.159 | Destabilizing | 0.994 | D | 0.77 | deleterious | None | None | None | None | N |
| P/D | 0.8038 | likely_pathogenic | 0.7642 | pathogenic | -1.825 | Destabilizing | 0.978 | D | 0.671 | neutral | None | None | None | None | N |
| P/E | 0.4731 | ambiguous | 0.4332 | ambiguous | -1.741 | Destabilizing | 0.956 | D | 0.63 | neutral | None | None | None | None | N |
| P/F | 0.7876 | likely_pathogenic | 0.7716 | pathogenic | -1.225 | Destabilizing | 0.978 | D | 0.792 | deleterious | None | None | None | None | N |
| P/G | 0.6125 | likely_pathogenic | 0.5792 | pathogenic | -2.132 | Highly Destabilizing | 0.754 | D | 0.591 | neutral | None | None | None | None | N |
| P/H | 0.4999 | ambiguous | 0.4321 | ambiguous | -1.643 | Destabilizing | 0.998 | D | 0.739 | prob.delet. | None | None | None | None | N |
| P/I | 0.3698 | ambiguous | 0.3782 | ambiguous | -0.711 | Destabilizing | 0.915 | D | 0.695 | prob.neutral | None | None | None | None | N |
| P/K | 0.5731 | likely_pathogenic | 0.4732 | ambiguous | -1.546 | Destabilizing | 0.956 | D | 0.633 | neutral | None | None | None | None | N |
| P/L | 0.2153 | likely_benign | 0.212 | benign | -0.711 | Destabilizing | 0.698 | D | 0.63 | neutral | N | 0.51715699 | None | None | N |
| P/M | 0.4144 | ambiguous | 0.4214 | ambiguous | -0.57 | Destabilizing | 0.994 | D | 0.749 | deleterious | None | None | None | None | N |
| P/N | 0.641 | likely_pathogenic | 0.6225 | pathogenic | -1.493 | Destabilizing | 0.978 | D | 0.75 | deleterious | None | None | None | None | N |
| P/Q | 0.2936 | likely_benign | 0.2536 | benign | -1.545 | Destabilizing | 0.97 | D | 0.69 | prob.neutral | N | 0.49157077 | None | None | N |
| P/R | 0.4777 | ambiguous | 0.3809 | ambiguous | -1.097 | Destabilizing | 0.97 | D | 0.749 | deleterious | N | 0.491722128 | None | None | N |
| P/S | 0.2628 | likely_benign | 0.2277 | benign | -2.024 | Highly Destabilizing | 0.698 | D | 0.553 | neutral | N | 0.492291559 | None | None | N |
| P/T | 0.2185 | likely_benign | 0.1971 | benign | -1.812 | Destabilizing | 0.822 | D | 0.575 | neutral | N | 0.503901354 | None | None | N |
| P/V | 0.2597 | likely_benign | 0.2566 | benign | -1.021 | Destabilizing | 0.16 | N | 0.432 | neutral | None | None | None | None | N |
| P/W | 0.9266 | likely_pathogenic | 0.915 | pathogenic | -1.512 | Destabilizing | 0.998 | D | 0.722 | prob.delet. | None | None | None | None | N |
| P/Y | 0.7669 | likely_pathogenic | 0.7203 | pathogenic | -1.192 | Destabilizing | 0.993 | D | 0.793 | deleterious | 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.