Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25543 | 76852;76853;76854 | chr2:178569505;178569504;178569503 | chr2:179434232;179434231;179434230 |
| N2AB | 23902 | 71929;71930;71931 | chr2:178569505;178569504;178569503 | chr2:179434232;179434231;179434230 |
| N2A | 22975 | 69148;69149;69150 | chr2:178569505;178569504;178569503 | chr2:179434232;179434231;179434230 |
| N2B | 16478 | 49657;49658;49659 | chr2:178569505;178569504;178569503 | chr2:179434232;179434231;179434230 |
| Novex-1 | 16603 | 50032;50033;50034 | chr2:178569505;178569504;178569503 | chr2:179434232;179434231;179434230 |
| Novex-2 | 16670 | 50233;50234;50235 | chr2:178569505;178569504;178569503 | chr2:179434232;179434231;179434230 |
| 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 | rs372016541  |
0.108 | 0.892 | N | 0.479 | 0.34 | None | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| K/E | rs372016541 |
0.108 | 0.892 | N | 0.479 | 0.34 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| K/E | rs372016541 |
0.108 | 0.892 | N | 0.479 | 0.34 | None | gnomAD-4.0.0 | 4.34098E-06 | None | None | None | None | N | None | 2.67158E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.24057E-06 | 0 | 0 |
| K/R | None | None | 0.892 | N | 0.495 | 0.238 | 0.425028116352 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31251E-06 | 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 | 0.4236 | ambiguous | 0.4327 | ambiguous | -0.204 | Destabilizing | 0.845 | D | 0.527 | neutral | None | None | None | None | N |
| K/C | 0.5791 | likely_pathogenic | 0.5846 | pathogenic | -0.382 | Destabilizing | 0.999 | D | 0.74 | deleterious | None | None | None | None | N |
| K/D | 0.7457 | likely_pathogenic | 0.749 | pathogenic | 0.184 | Stabilizing | 0.975 | D | 0.654 | neutral | None | None | None | None | N |
| K/E | 0.2553 | likely_benign | 0.2497 | benign | 0.251 | Stabilizing | 0.892 | D | 0.479 | neutral | N | 0.504158002 | None | None | N |
| K/F | 0.7376 | likely_pathogenic | 0.7393 | pathogenic | -0.081 | Destabilizing | 0.987 | D | 0.753 | deleterious | None | None | None | None | N |
| K/G | 0.652 | likely_pathogenic | 0.6633 | pathogenic | -0.502 | Destabilizing | 0.975 | D | 0.648 | neutral | None | None | None | None | N |
| K/H | 0.2509 | likely_benign | 0.2585 | benign | -0.749 | Destabilizing | 0.999 | D | 0.707 | prob.neutral | None | None | None | None | N |
| K/I | 0.2719 | likely_benign | 0.2629 | benign | 0.531 | Stabilizing | 0.967 | D | 0.731 | prob.delet. | N | 0.520303678 | None | None | N |
| K/L | 0.3442 | ambiguous | 0.3473 | ambiguous | 0.531 | Stabilizing | 0.845 | D | 0.609 | neutral | None | None | None | None | N |
| K/M | 0.2232 | likely_benign | 0.2244 | benign | 0.246 | Stabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | N |
| K/N | 0.4482 | ambiguous | 0.4441 | ambiguous | -0.068 | Destabilizing | 0.967 | D | 0.641 | neutral | N | 0.490669987 | None | None | N |
| K/P | 0.9775 | likely_pathogenic | 0.9801 | pathogenic | 0.317 | Stabilizing | 0.987 | D | 0.713 | prob.delet. | None | None | None | None | N |
| K/Q | 0.1275 | likely_benign | 0.1283 | benign | -0.162 | Destabilizing | 0.983 | D | 0.669 | neutral | D | 0.527805653 | None | None | N |
| K/R | 0.0858 | likely_benign | 0.0856 | benign | -0.281 | Destabilizing | 0.892 | D | 0.495 | neutral | N | 0.481822647 | None | None | N |
| K/S | 0.405 | ambiguous | 0.4108 | ambiguous | -0.664 | Destabilizing | 0.845 | D | 0.485 | neutral | None | None | None | None | N |
| K/T | 0.1301 | likely_benign | 0.131 | benign | -0.411 | Destabilizing | 0.025 | N | 0.483 | neutral | N | 0.449363512 | None | None | N |
| K/V | 0.2731 | likely_benign | 0.2709 | benign | 0.317 | Stabilizing | 0.95 | D | 0.643 | neutral | None | None | None | None | N |
| K/W | 0.77 | likely_pathogenic | 0.7773 | pathogenic | -0.014 | Destabilizing | 0.999 | D | 0.729 | prob.delet. | None | None | None | None | N |
| K/Y | 0.6292 | likely_pathogenic | 0.6411 | pathogenic | 0.296 | Stabilizing | 0.996 | D | 0.743 | deleterious | 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.