Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19926 | 60001;60002;60003 | chr2:178592128;178592127;178592126 | chr2:179456855;179456854;179456853 |
| N2AB | 18285 | 55078;55079;55080 | chr2:178592128;178592127;178592126 | chr2:179456855;179456854;179456853 |
| N2A | 17358 | 52297;52298;52299 | chr2:178592128;178592127;178592126 | chr2:179456855;179456854;179456853 |
| N2B | 10861 | 32806;32807;32808 | chr2:178592128;178592127;178592126 | chr2:179456855;179456854;179456853 |
| Novex-1 | 10986 | 33181;33182;33183 | chr2:178592128;178592127;178592126 | chr2:179456855;179456854;179456853 |
| Novex-2 | 11053 | 33382;33383;33384 | chr2:178592128;178592127;178592126 | chr2:179456855;179456854;179456853 |
| 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/H | rs2050345101  |
None | 0.999 | N | 0.711 | 0.334 | 0.519024713989 | gnomAD-4.0.0 | 1.59299E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8602E-06 | 0 | 0 |
| P/T | rs1433509946 |
-0.543 | 0.885 | N | 0.639 | 0.21 | 0.239901079897 | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | I | None | 0 | 2.91E-05 | None | 0 | 5.64E-05 | None | 0 | None | 0 | 0 | 0 |
| P/T | rs1433509946 |
-0.543 | 0.885 | N | 0.639 | 0.21 | 0.239901079897 | gnomAD-4.0.0 | 3.18602E-06 | None | None | None | None | I | None | 0 | 2.29064E-05 | None | 0 | 2.7894E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0614 | likely_benign | 0.0686 | benign | -0.572 | Destabilizing | 0.046 | N | 0.353 | neutral | N | 0.495834016 | None | None | I |
| P/C | 0.2924 | likely_benign | 0.3164 | benign | -0.587 | Destabilizing | 0.999 | D | 0.719 | prob.delet. | None | None | None | None | I |
| P/D | 0.4368 | ambiguous | 0.4567 | ambiguous | -0.272 | Destabilizing | 0.986 | D | 0.679 | prob.neutral | None | None | None | None | I |
| P/E | 0.2875 | likely_benign | 0.3105 | benign | -0.383 | Destabilizing | 0.986 | D | 0.669 | neutral | None | None | None | None | I |
| P/F | 0.3095 | likely_benign | 0.3408 | ambiguous | -0.749 | Destabilizing | 0.998 | D | 0.736 | prob.delet. | None | None | None | None | I |
| P/G | 0.2234 | likely_benign | 0.2575 | benign | -0.725 | Destabilizing | 0.91 | D | 0.567 | neutral | None | None | None | None | I |
| P/H | 0.1463 | likely_benign | 0.1676 | benign | -0.263 | Destabilizing | 0.999 | D | 0.711 | prob.delet. | N | 0.469643583 | None | None | I |
| P/I | 0.1656 | likely_benign | 0.1739 | benign | -0.316 | Destabilizing | 0.986 | D | 0.756 | deleterious | None | None | None | None | I |
| P/K | 0.2683 | likely_benign | 0.3166 | benign | -0.449 | Destabilizing | 0.986 | D | 0.667 | neutral | None | None | None | None | I |
| P/L | 0.0848 | likely_benign | 0.0914 | benign | -0.316 | Destabilizing | 0.982 | D | 0.671 | neutral | N | 0.502357343 | None | None | I |
| P/M | 0.2128 | likely_benign | 0.2237 | benign | -0.298 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | None | None | None | None | I |
| P/N | 0.2212 | likely_benign | 0.243 | benign | -0.154 | Destabilizing | 0.986 | D | 0.76 | deleterious | None | None | None | None | I |
| P/Q | 0.1274 | likely_benign | 0.1444 | benign | -0.415 | Destabilizing | 0.993 | D | 0.735 | prob.delet. | None | None | None | None | I |
| P/R | 0.1794 | likely_benign | 0.2097 | benign | 0.092 | Stabilizing | 0.982 | D | 0.748 | deleterious | N | 0.47878705 | None | None | I |
| P/S | 0.0848 | likely_benign | 0.0981 | benign | -0.555 | Destabilizing | 0.322 | N | 0.33 | neutral | N | 0.487251818 | None | None | I |
| P/T | 0.0774 | likely_benign | 0.0815 | benign | -0.563 | Destabilizing | 0.885 | D | 0.639 | neutral | N | 0.460142574 | None | None | I |
| P/V | 0.1156 | likely_benign | 0.1165 | benign | -0.365 | Destabilizing | 0.973 | D | 0.651 | neutral | None | None | None | None | I |
| P/W | 0.5094 | ambiguous | 0.5689 | pathogenic | -0.819 | Destabilizing | 0.999 | D | 0.691 | prob.neutral | None | None | None | None | I |
| P/Y | 0.2906 | likely_benign | 0.3238 | benign | -0.517 | Destabilizing | 0.999 | D | 0.737 | prob.delet. | 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.