Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20592 | 61999;62000;62001 | chr2:178589951;178589950;178589949 | chr2:179454678;179454677;179454676 |
| N2AB | 18951 | 57076;57077;57078 | chr2:178589951;178589950;178589949 | chr2:179454678;179454677;179454676 |
| N2A | 18024 | 54295;54296;54297 | chr2:178589951;178589950;178589949 | chr2:179454678;179454677;179454676 |
| N2B | 11527 | 34804;34805;34806 | chr2:178589951;178589950;178589949 | chr2:179454678;179454677;179454676 |
| Novex-1 | 11652 | 35179;35180;35181 | chr2:178589951;178589950;178589949 | chr2:179454678;179454677;179454676 |
| Novex-2 | 11719 | 35380;35381;35382 | chr2:178589951;178589950;178589949 | chr2:179454678;179454677;179454676 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/I | rs2049855196  |
None | 0.669 | N | 0.549 | 0.229 | 0.452546404249 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| N/K | rs554308191 |
-0.169 | 0.801 | N | 0.453 | 0.14 | 0.0666544352282 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| N/K | rs554308191 |
-0.169 | 0.801 | N | 0.453 | 0.14 | 0.0666544352282 | gnomAD-4.0.0 | 3.4223E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 5.79818E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.3373 | likely_benign | 0.3289 | benign | -0.778 | Destabilizing | 0.029 | N | 0.343 | neutral | None | None | None | None | N |
| N/C | 0.448 | ambiguous | 0.4121 | ambiguous | -0.079 | Destabilizing | 0.998 | D | 0.598 | neutral | None | None | None | None | N |
| N/D | 0.2345 | likely_benign | 0.2256 | benign | -0.477 | Destabilizing | 0.801 | D | 0.454 | neutral | N | 0.409081823 | None | None | N |
| N/E | 0.6145 | likely_pathogenic | 0.5617 | ambiguous | -0.356 | Destabilizing | 0.842 | D | 0.46 | neutral | None | None | None | None | N |
| N/F | 0.6671 | likely_pathogenic | 0.6557 | pathogenic | -0.597 | Destabilizing | 0.974 | D | 0.619 | neutral | None | None | None | None | N |
| N/G | 0.4788 | ambiguous | 0.4541 | ambiguous | -1.113 | Destabilizing | 0.525 | D | 0.437 | neutral | None | None | None | None | N |
| N/H | 0.2428 | likely_benign | 0.2237 | benign | -0.833 | Destabilizing | 0.989 | D | 0.512 | neutral | N | 0.422107048 | None | None | N |
| N/I | 0.2856 | likely_benign | 0.2859 | benign | 0.078 | Stabilizing | 0.669 | D | 0.549 | neutral | N | 0.410985977 | None | None | N |
| N/K | 0.6429 | likely_pathogenic | 0.5848 | pathogenic | -0.305 | Destabilizing | 0.801 | D | 0.453 | neutral | N | 0.369619357 | None | None | N |
| N/L | 0.3009 | likely_benign | 0.2903 | benign | 0.078 | Stabilizing | 0.525 | D | 0.497 | neutral | None | None | None | None | N |
| N/M | 0.3806 | ambiguous | 0.3649 | ambiguous | 0.239 | Stabilizing | 0.974 | D | 0.601 | neutral | None | None | None | None | N |
| N/P | 0.4094 | ambiguous | 0.4141 | ambiguous | -0.178 | Destabilizing | 0.974 | D | 0.629 | neutral | None | None | None | None | N |
| N/Q | 0.5835 | likely_pathogenic | 0.5326 | ambiguous | -0.731 | Destabilizing | 0.974 | D | 0.548 | neutral | None | None | None | None | N |
| N/R | 0.761 | likely_pathogenic | 0.7025 | pathogenic | -0.413 | Destabilizing | 0.842 | D | 0.537 | neutral | None | None | None | None | N |
| N/S | 0.1333 | likely_benign | 0.1289 | benign | -0.896 | Destabilizing | 0.051 | N | 0.13 | neutral | N | 0.394208371 | None | None | N |
| N/T | 0.2227 | likely_benign | 0.2189 | benign | -0.583 | Destabilizing | 0.454 | N | 0.473 | neutral | N | 0.408388389 | None | None | N |
| N/V | 0.3148 | likely_benign | 0.3121 | benign | -0.178 | Destabilizing | 0.067 | N | 0.442 | neutral | None | None | None | None | N |
| N/W | 0.894 | likely_pathogenic | 0.8771 | pathogenic | -0.476 | Destabilizing | 0.998 | D | 0.667 | neutral | None | None | None | None | N |
| N/Y | 0.2236 | likely_benign | 0.2102 | benign | -0.23 | Destabilizing | 0.989 | D | 0.613 | neutral | N | 0.478653764 | 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.