Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32346 | 97261;97262;97263 | chr2:178542818;178542817;178542816 | chr2:179407545;179407544;179407543 |
| N2AB | 30705 | 92338;92339;92340 | chr2:178542818;178542817;178542816 | chr2:179407545;179407544;179407543 |
| N2A | 29778 | 89557;89558;89559 | chr2:178542818;178542817;178542816 | chr2:179407545;179407544;179407543 |
| N2B | 23281 | 70066;70067;70068 | chr2:178542818;178542817;178542816 | chr2:179407545;179407544;179407543 |
| Novex-1 | 23406 | 70441;70442;70443 | chr2:178542818;178542817;178542816 | chr2:179407545;179407544;179407543 |
| Novex-2 | 23473 | 70642;70643;70644 | chr2:178542818;178542817;178542816 | chr2:179407545;179407544;179407543 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/Q | rs372803018  |
0.194 | 1.0 | N | 0.713 | 0.435 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| K/Q | rs372803018 |
0.194 | 1.0 | N | 0.713 | 0.435 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 1.44837E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| K/Q | rs372803018 |
0.194 | 1.0 | N | 0.713 | 0.435 | None | gnomAD-4.0.0 | 5.57732E-06 | None | None | None | None | N | None | 1.06818E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47608E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.3975 | ambiguous | 0.3111 | benign | -0.335 | Destabilizing | 0.999 | D | 0.67 | neutral | None | None | None | None | N |
| K/C | 0.7412 | likely_pathogenic | 0.655 | pathogenic | -0.475 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| K/D | 0.7734 | likely_pathogenic | 0.6549 | pathogenic | 0.488 | Stabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| K/E | 0.3071 | likely_benign | 0.2429 | benign | 0.554 | Stabilizing | 0.999 | D | 0.654 | neutral | N | 0.443880335 | None | None | N |
| K/F | 0.8154 | likely_pathogenic | 0.7385 | pathogenic | -0.33 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| K/G | 0.6098 | likely_pathogenic | 0.4763 | ambiguous | -0.597 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | N |
| K/H | 0.3834 | ambiguous | 0.3076 | benign | -0.745 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| K/I | 0.3811 | ambiguous | 0.3281 | benign | 0.297 | Stabilizing | 1.0 | D | 0.712 | prob.delet. | N | 0.470088288 | None | None | N |
| K/L | 0.3826 | ambiguous | 0.3217 | benign | 0.297 | Stabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | N |
| K/M | 0.312 | likely_benign | 0.2542 | benign | 0.006 | Stabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | N |
| K/N | 0.624 | likely_pathogenic | 0.5068 | ambiguous | -0.013 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | N | 0.473800597 | None | None | N |
| K/P | 0.3771 | ambiguous | 0.3376 | benign | 0.115 | Stabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | N |
| K/Q | 0.1727 | likely_benign | 0.1453 | benign | -0.078 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | N | 0.454521403 | None | None | N |
| K/R | 0.074 | likely_benign | 0.072 | benign | -0.116 | Destabilizing | 0.999 | D | 0.593 | neutral | N | 0.4450752 | None | None | N |
| K/S | 0.5548 | ambiguous | 0.4387 | ambiguous | -0.67 | Destabilizing | 0.999 | D | 0.66 | neutral | None | None | None | None | N |
| K/T | 0.2639 | likely_benign | 0.2032 | benign | -0.418 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | N | 0.456118913 | None | None | N |
| K/V | 0.3325 | likely_benign | 0.2793 | benign | 0.115 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| K/W | 0.8271 | likely_pathogenic | 0.746 | pathogenic | -0.265 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| K/Y | 0.7029 | likely_pathogenic | 0.6083 | pathogenic | 0.055 | Stabilizing | 1.0 | D | 0.686 | prob.neutral | 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.