Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19871 | 59836;59837;59838 | chr2:178592394;178592393;178592392 | chr2:179457121;179457120;179457119 |
| N2AB | 18230 | 54913;54914;54915 | chr2:178592394;178592393;178592392 | chr2:179457121;179457120;179457119 |
| N2A | 17303 | 52132;52133;52134 | chr2:178592394;178592393;178592392 | chr2:179457121;179457120;179457119 |
| N2B | 10806 | 32641;32642;32643 | chr2:178592394;178592393;178592392 | chr2:179457121;179457120;179457119 |
| Novex-1 | 10931 | 33016;33017;33018 | chr2:178592394;178592393;178592392 | chr2:179457121;179457120;179457119 |
| Novex-2 | 10998 | 33217;33218;33219 | chr2:178592394;178592393;178592392 | chr2:179457121;179457120;179457119 |
| 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/E | rs1475978640  |
0.106 | 0.959 | N | 0.476 | 0.299 | 0.367229591828 | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| K/E | rs1475978640 |
0.106 | 0.959 | N | 0.476 | 0.299 | 0.367229591828 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| K/E | rs1475978640 |
0.106 | 0.959 | N | 0.476 | 0.299 | 0.367229591828 | gnomAD-4.0.0 | 3.72028E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.08692E-06 | 0 | 0 |
| K/T | rs756249207 |
-0.673 | 0.061 | N | 0.235 | 0.243 | 0.300110245524 | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | N | None | 0 | 5.82E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| K/T | rs756249207 |
-0.673 | 0.061 | N | 0.235 | 0.243 | 0.300110245524 | gnomAD-4.0.0 | 3.18692E-06 | None | None | None | None | N | None | 0 | 4.58505E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.66 | likely_pathogenic | 0.7162 | pathogenic | -0.622 | Destabilizing | 0.863 | D | 0.483 | neutral | None | None | None | None | N |
| K/C | 0.8597 | likely_pathogenic | 0.8814 | pathogenic | -0.771 | Destabilizing | 0.999 | D | 0.585 | neutral | None | None | None | None | N |
| K/D | 0.7795 | likely_pathogenic | 0.8125 | pathogenic | -0.106 | Destabilizing | 0.969 | D | 0.57 | neutral | None | None | None | None | N |
| K/E | 0.4565 | ambiguous | 0.5473 | ambiguous | 0.03 | Stabilizing | 0.959 | D | 0.476 | neutral | N | 0.470506789 | None | None | N |
| K/F | 0.9304 | likely_pathogenic | 0.9431 | pathogenic | -0.206 | Destabilizing | 0.991 | D | 0.613 | neutral | None | None | None | None | N |
| K/G | 0.7731 | likely_pathogenic | 0.8134 | pathogenic | -1.007 | Destabilizing | 0.969 | D | 0.599 | neutral | None | None | None | None | N |
| K/H | 0.4241 | ambiguous | 0.445 | ambiguous | -1.232 | Destabilizing | 0.999 | D | 0.569 | neutral | None | None | None | None | N |
| K/I | 0.6737 | likely_pathogenic | 0.7281 | pathogenic | 0.383 | Stabilizing | 0.134 | N | 0.409 | neutral | N | 0.494714587 | None | None | N |
| K/L | 0.6327 | likely_pathogenic | 0.6791 | pathogenic | 0.383 | Stabilizing | 0.759 | D | 0.494 | neutral | None | None | None | None | N |
| K/M | 0.4736 | ambiguous | 0.5385 | ambiguous | 0.138 | Stabilizing | 0.991 | D | 0.586 | neutral | None | None | None | None | N |
| K/N | 0.5851 | likely_pathogenic | 0.6033 | pathogenic | -0.631 | Destabilizing | 0.959 | D | 0.527 | neutral | N | 0.437647796 | None | None | N |
| K/P | 0.8514 | likely_pathogenic | 0.8878 | pathogenic | 0.078 | Stabilizing | 0.997 | D | 0.603 | neutral | None | None | None | None | N |
| K/Q | 0.2765 | likely_benign | 0.3031 | benign | -0.646 | Destabilizing | 0.996 | D | 0.565 | neutral | N | 0.484612236 | None | None | N |
| K/R | 0.0981 | likely_benign | 0.1015 | benign | -0.637 | Destabilizing | 0.959 | D | 0.459 | neutral | N | 0.471760369 | None | None | N |
| K/S | 0.6668 | likely_pathogenic | 0.7076 | pathogenic | -1.315 | Destabilizing | 0.759 | D | 0.447 | neutral | None | None | None | None | N |
| K/T | 0.3564 | ambiguous | 0.413 | ambiguous | -0.963 | Destabilizing | 0.061 | N | 0.235 | neutral | N | 0.425025215 | None | None | N |
| K/V | 0.6171 | likely_pathogenic | 0.6741 | pathogenic | 0.078 | Stabilizing | 0.759 | D | 0.496 | neutral | None | None | None | None | N |
| K/W | 0.8906 | likely_pathogenic | 0.9155 | pathogenic | -0.076 | Destabilizing | 0.999 | D | 0.605 | neutral | None | None | None | None | N |
| K/Y | 0.8178 | likely_pathogenic | 0.8506 | pathogenic | 0.217 | Stabilizing | 0.997 | D | 0.616 | 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.