Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23153 | 69682;69683;69684 | chr2:178576787;178576786;178576785 | chr2:179441514;179441513;179441512 |
| N2AB | 21512 | 64759;64760;64761 | chr2:178576787;178576786;178576785 | chr2:179441514;179441513;179441512 |
| N2A | 20585 | 61978;61979;61980 | chr2:178576787;178576786;178576785 | chr2:179441514;179441513;179441512 |
| N2B | 14088 | 42487;42488;42489 | chr2:178576787;178576786;178576785 | chr2:179441514;179441513;179441512 |
| Novex-1 | 14213 | 42862;42863;42864 | chr2:178576787;178576786;178576785 | chr2:179441514;179441513;179441512 |
| Novex-2 | 14280 | 43063;43064;43065 | chr2:178576787;178576786;178576785 | chr2:179441514;179441513;179441512 |
| 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/R | None | None | 0.026 | N | 0.144 | 0.105 | 0.285698343383 | gnomAD-4.0.0 | 6.84355E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99578E-07 | 0 | 0 |
| K/T | rs879119970  |
-0.498 | 0.811 | N | 0.521 | 0.161 | None | gnomAD-2.1.1 | 2.15E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.71E-05 | 0 |
| K/T | rs879119970 |
-0.498 | 0.811 | N | 0.521 | 0.161 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| K/T | rs879119970 |
-0.498 | 0.811 | N | 0.521 | 0.161 | None | gnomAD-4.0.0 | 1.98351E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.71274E-05 | 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 | 0.3899 | ambiguous | 0.3814 | ambiguous | -0.319 | Destabilizing | 0.851 | D | 0.537 | neutral | None | None | None | None | N |
| K/C | 0.7498 | likely_pathogenic | 0.7289 | pathogenic | -0.499 | Destabilizing | 0.999 | D | 0.731 | prob.delet. | None | None | None | None | N |
| K/D | 0.8441 | likely_pathogenic | 0.8688 | pathogenic | -0.527 | Destabilizing | 0.976 | D | 0.517 | neutral | None | None | None | None | N |
| K/E | 0.3725 | ambiguous | 0.4071 | ambiguous | -0.499 | Destabilizing | 0.896 | D | 0.495 | neutral | N | 0.471821005 | None | None | N |
| K/F | 0.9304 | likely_pathogenic | 0.9342 | pathogenic | -0.506 | Destabilizing | 0.996 | D | 0.689 | prob.neutral | None | None | None | None | N |
| K/G | 0.381 | ambiguous | 0.3693 | ambiguous | -0.585 | Destabilizing | 0.851 | D | 0.549 | neutral | None | None | None | None | N |
| K/H | 0.5255 | ambiguous | 0.5281 | ambiguous | -1.053 | Destabilizing | 0.999 | D | 0.539 | neutral | None | None | None | None | N |
| K/I | 0.7092 | likely_pathogenic | 0.733 | pathogenic | 0.324 | Stabilizing | 0.988 | D | 0.685 | prob.neutral | None | None | None | None | N |
| K/L | 0.6573 | likely_pathogenic | 0.6811 | pathogenic | 0.324 | Stabilizing | 0.919 | D | 0.533 | neutral | None | None | None | None | N |
| K/M | 0.4603 | ambiguous | 0.4805 | ambiguous | 0.435 | Stabilizing | 0.999 | D | 0.531 | neutral | N | 0.490727261 | None | None | N |
| K/N | 0.6849 | likely_pathogenic | 0.7195 | pathogenic | -0.273 | Destabilizing | 0.896 | D | 0.463 | neutral | N | 0.49923968 | None | None | N |
| K/P | 0.8224 | likely_pathogenic | 0.8217 | pathogenic | 0.139 | Stabilizing | 0.988 | D | 0.553 | neutral | None | None | None | None | N |
| K/Q | 0.1973 | likely_benign | 0.2024 | benign | -0.583 | Destabilizing | 0.968 | D | 0.535 | neutral | N | 0.503704137 | None | None | N |
| K/R | 0.0773 | likely_benign | 0.0736 | benign | -0.313 | Destabilizing | 0.026 | N | 0.144 | neutral | N | 0.421549688 | None | None | N |
| K/S | 0.5042 | ambiguous | 0.5093 | ambiguous | -0.81 | Destabilizing | 0.261 | N | 0.263 | neutral | None | None | None | None | N |
| K/T | 0.4311 | ambiguous | 0.4635 | ambiguous | -0.621 | Destabilizing | 0.811 | D | 0.521 | neutral | N | 0.500970476 | None | None | N |
| K/V | 0.6111 | likely_pathogenic | 0.6315 | pathogenic | 0.139 | Stabilizing | 0.976 | D | 0.56 | neutral | None | None | None | None | N |
| K/W | 0.8895 | likely_pathogenic | 0.8833 | pathogenic | -0.415 | Destabilizing | 0.999 | D | 0.748 | deleterious | None | None | None | None | N |
| K/Y | 0.8419 | likely_pathogenic | 0.8437 | pathogenic | -0.037 | Destabilizing | 0.996 | D | 0.651 | 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.