Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18399 | 55420;55421;55422 | chr2:178602076;178602075;178602074 | chr2:179466803;179466802;179466801 |
| N2AB | 16758 | 50497;50498;50499 | chr2:178602076;178602075;178602074 | chr2:179466803;179466802;179466801 |
| N2A | 15831 | 47716;47717;47718 | chr2:178602076;178602075;178602074 | chr2:179466803;179466802;179466801 |
| N2B | 9334 | 28225;28226;28227 | chr2:178602076;178602075;178602074 | chr2:179466803;179466802;179466801 |
| Novex-1 | 9459 | 28600;28601;28602 | chr2:178602076;178602075;178602074 | chr2:179466803;179466802;179466801 |
| Novex-2 | 9526 | 28801;28802;28803 | chr2:178602076;178602075;178602074 | chr2:179466803;179466802;179466801 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/S | rs774591174  |
-0.79 | 0.987 | N | 0.76 | 0.356 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| P/S | rs774591174 |
-0.79 | 0.987 | N | 0.76 | 0.356 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs774591174 |
-0.79 | 0.987 | N | 0.76 | 0.356 | None | gnomAD-4.0.0 | 1.0542E-05 | None | None | None | None | I | None | 1.33643E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.35683E-05 | 0 | 0 |
| P/T | None | None | 0.568 | N | 0.383 | 0.297 | 0.461845970543 | gnomAD-4.0.0 | 4.79225E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.29896E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.2044 | likely_benign | 0.202 | benign | -0.921 | Destabilizing | 0.955 | D | 0.622 | neutral | N | 0.50342819 | None | None | I |
| P/C | 0.7351 | likely_pathogenic | 0.7393 | pathogenic | -0.833 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | I |
| P/D | 0.7672 | likely_pathogenic | 0.8063 | pathogenic | -0.579 | Destabilizing | 0.995 | D | 0.849 | deleterious | None | None | None | None | I |
| P/E | 0.5791 | likely_pathogenic | 0.6288 | pathogenic | -0.61 | Destabilizing | 0.995 | D | 0.834 | deleterious | None | None | None | None | I |
| P/F | 0.7553 | likely_pathogenic | 0.7352 | pathogenic | -0.698 | Destabilizing | 0.999 | D | 0.846 | deleterious | None | None | None | None | I |
| P/G | 0.5911 | likely_pathogenic | 0.6174 | pathogenic | -1.171 | Destabilizing | 0.995 | D | 0.765 | deleterious | None | None | None | None | I |
| P/H | 0.4229 | ambiguous | 0.4473 | ambiguous | -0.588 | Destabilizing | 1.0 | D | 0.825 | deleterious | N | 0.487098362 | None | None | I |
| P/I | 0.5632 | ambiguous | 0.5168 | ambiguous | -0.363 | Destabilizing | 0.995 | D | 0.86 | deleterious | None | None | None | None | I |
| P/K | 0.5577 | ambiguous | 0.5986 | pathogenic | -0.877 | Destabilizing | 0.995 | D | 0.848 | deleterious | None | None | None | None | I |
| P/L | 0.2556 | likely_benign | 0.2525 | benign | -0.363 | Destabilizing | 0.987 | D | 0.808 | deleterious | N | 0.481564953 | None | None | I |
| P/M | 0.5667 | likely_pathogenic | 0.545 | ambiguous | -0.481 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | I |
| P/N | 0.6063 | likely_pathogenic | 0.6162 | pathogenic | -0.704 | Destabilizing | 0.995 | D | 0.827 | deleterious | None | None | None | None | I |
| P/Q | 0.4019 | ambiguous | 0.4245 | ambiguous | -0.853 | Destabilizing | 0.998 | D | 0.868 | deleterious | None | None | None | None | I |
| P/R | 0.3869 | ambiguous | 0.4288 | ambiguous | -0.374 | Destabilizing | 0.997 | D | 0.847 | deleterious | N | 0.503681679 | None | None | I |
| P/S | 0.3141 | likely_benign | 0.3291 | benign | -1.17 | Destabilizing | 0.987 | D | 0.76 | deleterious | N | 0.5195301 | None | None | I |
| P/T | 0.2343 | likely_benign | 0.2334 | benign | -1.086 | Destabilizing | 0.568 | D | 0.383 | neutral | N | 0.502309776 | None | None | I |
| P/V | 0.3947 | ambiguous | 0.3691 | ambiguous | -0.513 | Destabilizing | 0.99 | D | 0.756 | deleterious | None | None | None | None | I |
| P/W | 0.8705 | likely_pathogenic | 0.8789 | pathogenic | -0.835 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | I |
| P/Y | 0.7165 | likely_pathogenic | 0.7196 | pathogenic | -0.546 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | I |
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.