Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20433 | 61522;61523;61524 | chr2:178590428;178590427;178590426 | chr2:179455155;179455154;179455153 |
| N2AB | 18792 | 56599;56600;56601 | chr2:178590428;178590427;178590426 | chr2:179455155;179455154;179455153 |
| N2A | 17865 | 53818;53819;53820 | chr2:178590428;178590427;178590426 | chr2:179455155;179455154;179455153 |
| N2B | 11368 | 34327;34328;34329 | chr2:178590428;178590427;178590426 | chr2:179455155;179455154;179455153 |
| Novex-1 | 11493 | 34702;34703;34704 | chr2:178590428;178590427;178590426 | chr2:179455155;179455154;179455153 |
| Novex-2 | 11560 | 34903;34904;34905 | chr2:178590428;178590427;178590426 | chr2:179455155;179455154;179455153 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/M | rs1475658626  |
None | 0.963 | N | 0.571 | 0.357 | 0.433047596574 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/M | rs1475658626 |
None | 0.963 | N | 0.571 | 0.357 | 0.433047596574 | gnomAD-4.0.0 | 6.5767E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47119E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5974 | likely_pathogenic | 0.6008 | pathogenic | -0.423 | Destabilizing | 0.25 | N | 0.504 | neutral | None | None | None | None | N |
| R/C | 0.2231 | likely_benign | 0.2668 | benign | -0.443 | Destabilizing | 0.992 | D | 0.593 | neutral | None | None | None | None | N |
| R/D | 0.9117 | likely_pathogenic | 0.9229 | pathogenic | -0.025 | Destabilizing | 0.617 | D | 0.593 | neutral | None | None | None | None | N |
| R/E | 0.5982 | likely_pathogenic | 0.6218 | pathogenic | 0.098 | Stabilizing | 0.447 | N | 0.545 | neutral | None | None | None | None | N |
| R/F | 0.8555 | likely_pathogenic | 0.8615 | pathogenic | -0.38 | Destabilizing | 0.92 | D | 0.585 | neutral | None | None | None | None | N |
| R/G | 0.6083 | likely_pathogenic | 0.6199 | pathogenic | -0.709 | Destabilizing | 0.549 | D | 0.559 | neutral | N | 0.46668475 | None | None | N |
| R/H | 0.1499 | likely_benign | 0.165 | benign | -1.277 | Destabilizing | 0.92 | D | 0.575 | neutral | None | None | None | None | N |
| R/I | 0.4536 | ambiguous | 0.4448 | ambiguous | 0.33 | Stabilizing | 0.85 | D | 0.611 | neutral | None | None | None | None | N |
| R/K | 0.1633 | likely_benign | 0.1611 | benign | -0.406 | Destabilizing | 0.004 | N | 0.251 | neutral | N | 0.451581806 | None | None | N |
| R/L | 0.4514 | ambiguous | 0.4629 | ambiguous | 0.33 | Stabilizing | 0.447 | N | 0.571 | neutral | None | None | None | None | N |
| R/M | 0.526 | ambiguous | 0.523 | ambiguous | -0.139 | Destabilizing | 0.963 | D | 0.571 | neutral | N | 0.51763344 | None | None | N |
| R/N | 0.7958 | likely_pathogenic | 0.8122 | pathogenic | -0.097 | Destabilizing | 0.617 | D | 0.541 | neutral | None | None | None | None | N |
| R/P | 0.8007 | likely_pathogenic | 0.8264 | pathogenic | 0.101 | Stabilizing | 0.92 | D | 0.617 | neutral | None | None | None | None | N |
| R/Q | 0.1396 | likely_benign | 0.1498 | benign | -0.162 | Destabilizing | 0.127 | N | 0.381 | neutral | None | None | None | None | N |
| R/S | 0.6483 | likely_pathogenic | 0.6644 | pathogenic | -0.659 | Destabilizing | 0.379 | N | 0.543 | neutral | N | 0.492601709 | None | None | N |
| R/T | 0.2903 | likely_benign | 0.2749 | benign | -0.355 | Destabilizing | 0.002 | N | 0.277 | neutral | N | 0.400032691 | None | None | N |
| R/V | 0.4715 | ambiguous | 0.4704 | ambiguous | 0.101 | Stabilizing | 0.447 | N | 0.573 | neutral | None | None | None | None | N |
| R/W | 0.4331 | ambiguous | 0.4452 | ambiguous | -0.229 | Destabilizing | 0.99 | D | 0.634 | neutral | N | 0.478294545 | None | None | N |
| R/Y | 0.7219 | likely_pathogenic | 0.743 | pathogenic | 0.117 | Stabilizing | 0.972 | D | 0.596 | 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.