Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32692 | 98299;98300;98301 | chr2:178540092;178540091;178540090 | chr2:179404819;179404818;179404817 |
| N2AB | 31051 | 93376;93377;93378 | chr2:178540092;178540091;178540090 | chr2:179404819;179404818;179404817 |
| N2A | 30124 | 90595;90596;90597 | chr2:178540092;178540091;178540090 | chr2:179404819;179404818;179404817 |
| N2B | 23627 | 71104;71105;71106 | chr2:178540092;178540091;178540090 | chr2:179404819;179404818;179404817 |
| Novex-1 | 23752 | 71479;71480;71481 | chr2:178540092;178540091;178540090 | chr2:179404819;179404818;179404817 |
| Novex-2 | 23819 | 71680;71681;71682 | chr2:178540092;178540091;178540090 | chr2:179404819;179404818;179404817 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs727505311  |
None | 0.451 | N | 0.658 | 0.161 | 0.427254322456 | gnomAD-4.0.0 | 6.87862E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.66633E-05 |
| T/R | rs727505311 |
-0.302 | 0.966 | N | 0.71 | 0.219 | 0.673120225707 | gnomAD-2.1.1 | 3.27E-05 | None | None | None | None | N | None | 0 | 0 | None | 5.26316E-04 | 0 | None | 0 | None | 0 | 2.71E-05 | 0 |
| T/R | rs727505311 |
-0.302 | 0.966 | N | 0.71 | 0.219 | 0.673120225707 | gnomAD-4.0.0 | 1.92601E-05 | None | None | None | None | N | None | 0 | 0 | None | 5.46491E-04 | 0 | None | 0 | 0 | 1.26502E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0839 | likely_benign | 0.0891 | benign | -0.485 | Destabilizing | 0.451 | N | 0.459 | neutral | N | 0.452670389 | None | None | N |
| T/C | 0.3306 | likely_benign | 0.3465 | ambiguous | -0.375 | Destabilizing | 0.998 | D | 0.681 | prob.neutral | None | None | None | None | N |
| T/D | 0.3812 | ambiguous | 0.4093 | ambiguous | 0.299 | Stabilizing | 0.991 | D | 0.669 | prob.neutral | None | None | None | None | N |
| T/E | 0.2951 | likely_benign | 0.3259 | benign | 0.243 | Stabilizing | 0.974 | D | 0.678 | prob.neutral | None | None | None | None | N |
| T/F | 0.2253 | likely_benign | 0.2462 | benign | -0.83 | Destabilizing | 0.949 | D | 0.825 | deleterious | None | None | None | None | N |
| T/G | 0.336 | likely_benign | 0.3457 | ambiguous | -0.651 | Destabilizing | 0.915 | D | 0.763 | deleterious | None | None | None | None | N |
| T/H | 0.2567 | likely_benign | 0.2815 | benign | -0.855 | Destabilizing | 0.998 | D | 0.797 | deleterious | None | None | None | None | N |
| T/I | 0.0899 | likely_benign | 0.0934 | benign | -0.16 | Destabilizing | 0.451 | N | 0.658 | prob.neutral | N | 0.485513526 | None | None | N |
| T/K | 0.1813 | likely_benign | 0.2037 | benign | -0.425 | Destabilizing | 0.966 | D | 0.675 | prob.neutral | N | 0.416443017 | None | None | N |
| T/L | 0.0903 | likely_benign | 0.0961 | benign | -0.16 | Destabilizing | 0.522 | D | 0.563 | neutral | None | None | None | None | N |
| T/M | 0.0822 | likely_benign | 0.0877 | benign | -0.055 | Destabilizing | 0.974 | D | 0.705 | prob.delet. | None | None | None | None | N |
| T/N | 0.134 | likely_benign | 0.1389 | benign | -0.237 | Destabilizing | 0.991 | D | 0.546 | neutral | None | None | None | None | N |
| T/P | 0.0944 | likely_benign | 0.1018 | benign | -0.238 | Destabilizing | 0.989 | D | 0.694 | prob.delet. | N | 0.358357506 | None | None | N |
| T/Q | 0.23 | likely_benign | 0.2496 | benign | -0.438 | Destabilizing | 0.991 | D | 0.693 | prob.delet. | None | None | None | None | N |
| T/R | 0.1682 | likely_benign | 0.1935 | benign | -0.147 | Destabilizing | 0.966 | D | 0.71 | prob.delet. | N | 0.478395553 | None | None | N |
| T/S | 0.1377 | likely_benign | 0.141 | benign | -0.512 | Destabilizing | 0.89 | D | 0.554 | neutral | N | 0.416096301 | None | None | N |
| T/V | 0.0847 | likely_benign | 0.0867 | benign | -0.238 | Destabilizing | 0.007 | N | 0.169 | neutral | None | None | None | None | N |
| T/W | 0.5599 | ambiguous | 0.6106 | pathogenic | -0.794 | Destabilizing | 0.998 | D | 0.815 | deleterious | None | None | None | None | N |
| T/Y | 0.2741 | likely_benign | 0.3042 | benign | -0.531 | Destabilizing | 0.974 | D | 0.809 | 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.