Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18326 | 55201;55202;55203 | chr2:178602426;178602425;178602424 | chr2:179467153;179467152;179467151 |
| N2AB | 16685 | 50278;50279;50280 | chr2:178602426;178602425;178602424 | chr2:179467153;179467152;179467151 |
| N2A | 15758 | 47497;47498;47499 | chr2:178602426;178602425;178602424 | chr2:179467153;179467152;179467151 |
| N2B | 9261 | 28006;28007;28008 | chr2:178602426;178602425;178602424 | chr2:179467153;179467152;179467151 |
| Novex-1 | 9386 | 28381;28382;28383 | chr2:178602426;178602425;178602424 | chr2:179467153;179467152;179467151 |
| Novex-2 | 9453 | 28582;28583;28584 | chr2:178602426;178602425;178602424 | chr2:179467153;179467152;179467151 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | None | None | 0.619 | N | 0.311 | 0.074 | 0.29908675 | gnomAD-4.0.0 | 1.59353E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86202E-06 | 0 | 0 |
| D/G | None | None | 0.996 | N | 0.585 | 0.435 | 0.31381804 | gnomAD-4.0.0 | 1.59352E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43349E-05 | 0 |
| D/N | rs1553675887  |
None | 0.999 | N | 0.679 | 0.359 | 0.2704478 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1171 | likely_benign | 0.1228 | benign | 0.012 | Stabilizing | 0.998 | D | 0.553 | neutral | N | 0.4788057 | None | None | N |
| D/C | 0.4153 | ambiguous | 0.4594 | ambiguous | -0.2 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | N |
| D/E | 0.0899 | likely_benign | 0.0941 | benign | -0.298 | Destabilizing | 0.619 | D | 0.311 | neutral | N | 0.46901277 | None | None | N |
| D/F | 0.4981 | ambiguous | 0.5312 | ambiguous | -0.097 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| D/G | 0.0798 | likely_benign | 0.0825 | benign | -0.095 | Destabilizing | 0.996 | D | 0.585 | neutral | N | 0.49079075 | None | None | N |
| D/H | 0.1815 | likely_benign | 0.1826 | benign | 0.521 | Stabilizing | 1.0 | D | 0.654 | neutral | N | 0.52111644 | None | None | N |
| D/I | 0.2872 | likely_benign | 0.3344 | benign | 0.227 | Stabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| D/K | 0.2059 | likely_benign | 0.2274 | benign | 0.343 | Stabilizing | 0.998 | D | 0.602 | neutral | None | None | None | None | N |
| D/L | 0.2514 | likely_benign | 0.298 | benign | 0.227 | Stabilizing | 0.999 | D | 0.684 | prob.neutral | None | None | None | None | N |
| D/M | 0.4476 | ambiguous | 0.5026 | ambiguous | -0.006 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| D/N | 0.0735 | likely_benign | 0.0864 | benign | 0.171 | Stabilizing | 0.999 | D | 0.679 | prob.neutral | N | 0.48571303 | None | None | N |
| D/P | 0.4548 | ambiguous | 0.5176 | ambiguous | 0.174 | Stabilizing | 1.0 | D | 0.623 | neutral | None | None | None | None | N |
| D/Q | 0.1827 | likely_benign | 0.1927 | benign | 0.161 | Stabilizing | 0.998 | D | 0.689 | prob.neutral | None | None | None | None | N |
| D/R | 0.2583 | likely_benign | 0.2694 | benign | 0.596 | Stabilizing | 0.998 | D | 0.653 | neutral | None | None | None | None | N |
| D/S | 0.0894 | likely_benign | 0.0963 | benign | 0.051 | Stabilizing | 0.994 | D | 0.617 | neutral | None | None | None | None | N |
| D/T | 0.1697 | likely_benign | 0.1835 | benign | 0.138 | Stabilizing | 0.999 | D | 0.626 | neutral | None | None | None | None | N |
| D/V | 0.1714 | likely_benign | 0.1941 | benign | 0.174 | Stabilizing | 0.999 | D | 0.679 | prob.neutral | N | 0.46428174 | None | None | N |
| D/W | 0.7325 | likely_pathogenic | 0.7557 | pathogenic | -0.065 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| D/Y | 0.1923 | likely_benign | 0.2054 | benign | 0.124 | Stabilizing | 1.0 | D | 0.696 | prob.neutral | N | 0.51519054 | 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.