Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24224 | 72895;72896;72897 | chr2:178573462;178573461;178573460 | chr2:179438189;179438188;179438187 |
| N2AB | 22583 | 67972;67973;67974 | chr2:178573462;178573461;178573460 | chr2:179438189;179438188;179438187 |
| N2A | 21656 | 65191;65192;65193 | chr2:178573462;178573461;178573460 | chr2:179438189;179438188;179438187 |
| N2B | 15159 | 45700;45701;45702 | chr2:178573462;178573461;178573460 | chr2:179438189;179438188;179438187 |
| Novex-1 | 15284 | 46075;46076;46077 | chr2:178573462;178573461;178573460 | chr2:179438189;179438188;179438187 |
| Novex-2 | 15351 | 46276;46277;46278 | chr2:178573462;178573461;178573460 | chr2:179438189;179438188;179438187 |
| 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/N | rs775487933  |
-0.343 | 0.892 | N | 0.569 | 0.249 | 0.430694319191 | gnomAD-2.1.1 | 5.78E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.17E-05 | 0 |
| D/N | rs775487933 |
-0.343 | 0.892 | N | 0.569 | 0.249 | 0.430694319191 | gnomAD-4.0.0 | 5.13683E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.55863E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1062 | likely_benign | 0.1123 | benign | -0.229 | Destabilizing | 0.805 | D | 0.622 | neutral | N | 0.500842572 | None | None | N |
| D/C | 0.4698 | ambiguous | 0.5008 | ambiguous | 0.089 | Stabilizing | 0.999 | D | 0.735 | prob.delet. | None | None | None | None | N |
| D/E | 0.1681 | likely_benign | 0.1797 | benign | -0.735 | Destabilizing | 0.892 | D | 0.545 | neutral | N | 0.473116758 | None | None | N |
| D/F | 0.4678 | ambiguous | 0.4961 | ambiguous | -0.416 | Destabilizing | 0.987 | D | 0.753 | deleterious | None | None | None | None | N |
| D/G | 0.1036 | likely_benign | 0.1045 | benign | -0.5 | Destabilizing | 0.805 | D | 0.551 | neutral | N | 0.436711141 | None | None | N |
| D/H | 0.2515 | likely_benign | 0.2762 | benign | -0.781 | Destabilizing | 0.999 | D | 0.623 | neutral | N | 0.514480283 | None | None | N |
| D/I | 0.3888 | ambiguous | 0.4085 | ambiguous | 0.451 | Stabilizing | 0.975 | D | 0.72 | prob.delet. | None | None | None | None | N |
| D/K | 0.3699 | ambiguous | 0.4064 | ambiguous | -0.048 | Destabilizing | 0.975 | D | 0.604 | neutral | None | None | None | None | N |
| D/L | 0.2496 | likely_benign | 0.2727 | benign | 0.451 | Stabilizing | 0.95 | D | 0.686 | prob.neutral | None | None | None | None | N |
| D/M | 0.4906 | ambiguous | 0.523 | ambiguous | 0.847 | Stabilizing | 0.999 | D | 0.735 | prob.delet. | None | None | None | None | N |
| D/N | 0.0977 | likely_benign | 0.1016 | benign | -0.276 | Destabilizing | 0.892 | D | 0.569 | neutral | N | 0.479232824 | None | None | N |
| D/P | 0.8797 | likely_pathogenic | 0.8677 | pathogenic | 0.25 | Stabilizing | 0.987 | D | 0.583 | neutral | None | None | None | None | N |
| D/Q | 0.3014 | likely_benign | 0.3306 | benign | -0.22 | Destabilizing | 0.975 | D | 0.535 | neutral | None | None | None | None | N |
| D/R | 0.449 | ambiguous | 0.4726 | ambiguous | -0.086 | Destabilizing | 0.975 | D | 0.685 | prob.neutral | None | None | None | None | N |
| D/S | 0.0775 | likely_benign | 0.0811 | benign | -0.449 | Destabilizing | 0.128 | N | 0.381 | neutral | None | None | None | None | N |
| D/T | 0.1929 | likely_benign | 0.2035 | benign | -0.241 | Destabilizing | 0.128 | N | 0.481 | neutral | None | None | None | None | N |
| D/V | 0.234 | likely_benign | 0.2482 | benign | 0.25 | Stabilizing | 0.935 | D | 0.682 | prob.neutral | N | 0.513973304 | None | None | N |
| D/W | 0.8953 | likely_pathogenic | 0.9099 | pathogenic | -0.427 | Destabilizing | 0.999 | D | 0.736 | prob.delet. | None | None | None | None | N |
| D/Y | 0.2203 | likely_benign | 0.2369 | benign | -0.212 | Destabilizing | 0.994 | D | 0.752 | deleterious | N | 0.514226793 | 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.