Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19963 | 60112;60113;60114 | chr2:178592017;178592016;178592015 | chr2:179456744;179456743;179456742 |
| N2AB | 18322 | 55189;55190;55191 | chr2:178592017;178592016;178592015 | chr2:179456744;179456743;179456742 |
| N2A | 17395 | 52408;52409;52410 | chr2:178592017;178592016;178592015 | chr2:179456744;179456743;179456742 |
| N2B | 10898 | 32917;32918;32919 | chr2:178592017;178592016;178592015 | chr2:179456744;179456743;179456742 |
| Novex-1 | 11023 | 33292;33293;33294 | chr2:178592017;178592016;178592015 | chr2:179456744;179456743;179456742 |
| Novex-2 | 11090 | 33493;33494;33495 | chr2:178592017;178592016;178592015 | chr2:179456744;179456743;179456742 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1553645836  |
None | 0.332 | N | 0.597 | 0.137 | 0.32053947749 | gnomAD-4.0.0 | 4.80129E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.25001E-06 | 0 | 0 |
| V/I | rs768578399 |
-0.331 | 0.004 | N | 0.207 | 0.064 | 0.340032825777 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| V/I | rs768578399 |
-0.331 | 0.004 | N | 0.207 | 0.064 | 0.340032825777 | gnomAD-4.0.0 | 1.36913E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7994E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1483 | likely_benign | 0.1408 | benign | -1.513 | Destabilizing | 0.332 | N | 0.597 | neutral | N | 0.451501661 | None | None | N |
| V/C | 0.6607 | likely_pathogenic | 0.6652 | pathogenic | -0.876 | Destabilizing | 0.992 | D | 0.647 | neutral | None | None | None | None | N |
| V/D | 0.6993 | likely_pathogenic | 0.7062 | pathogenic | -1.582 | Destabilizing | 0.895 | D | 0.827 | deleterious | N | 0.471667819 | None | None | N |
| V/E | 0.4808 | ambiguous | 0.4823 | ambiguous | -1.501 | Destabilizing | 0.919 | D | 0.636 | neutral | None | None | None | None | N |
| V/F | 0.3204 | likely_benign | 0.3133 | benign | -0.945 | Destabilizing | 0.808 | D | 0.648 | neutral | N | 0.485768951 | None | None | N |
| V/G | 0.3465 | ambiguous | 0.3275 | benign | -1.907 | Destabilizing | 0.895 | D | 0.73 | deleterious | N | 0.494580435 | None | None | N |
| V/H | 0.7071 | likely_pathogenic | 0.7018 | pathogenic | -1.562 | Destabilizing | 0.992 | D | 0.856 | deleterious | None | None | None | None | N |
| V/I | 0.086 | likely_benign | 0.0904 | benign | -0.494 | Destabilizing | 0.004 | N | 0.207 | neutral | N | 0.489635975 | None | None | N |
| V/K | 0.4851 | ambiguous | 0.4749 | ambiguous | -1.33 | Destabilizing | 0.919 | D | 0.644 | neutral | None | None | None | None | N |
| V/L | 0.2346 | likely_benign | 0.2485 | benign | -0.494 | Destabilizing | 0.079 | N | 0.541 | neutral | N | 0.431838465 | None | None | N |
| V/M | 0.1892 | likely_benign | 0.1918 | benign | -0.38 | Destabilizing | 0.848 | D | 0.531 | neutral | None | None | None | None | N |
| V/N | 0.5282 | ambiguous | 0.5326 | ambiguous | -1.256 | Destabilizing | 0.919 | D | 0.837 | deleterious | None | None | None | None | N |
| V/P | 0.9402 | likely_pathogenic | 0.9307 | pathogenic | -0.801 | Destabilizing | 0.972 | D | 0.733 | deleterious | None | None | None | None | N |
| V/Q | 0.385 | ambiguous | 0.3712 | ambiguous | -1.305 | Destabilizing | 0.972 | D | 0.755 | deleterious | None | None | None | None | N |
| V/R | 0.3746 | ambiguous | 0.3536 | ambiguous | -0.944 | Destabilizing | 0.919 | D | 0.835 | deleterious | None | None | None | None | N |
| V/S | 0.2508 | likely_benign | 0.2427 | benign | -1.786 | Destabilizing | 0.737 | D | 0.611 | neutral | None | None | None | None | N |
| V/T | 0.1336 | likely_benign | 0.1314 | benign | -1.594 | Destabilizing | 0.047 | N | 0.499 | neutral | None | None | None | None | N |
| V/W | 0.8989 | likely_pathogenic | 0.8966 | pathogenic | -1.308 | Destabilizing | 0.992 | D | 0.791 | deleterious | None | None | None | None | N |
| V/Y | 0.7443 | likely_pathogenic | 0.7454 | pathogenic | -0.947 | Destabilizing | 0.919 | D | 0.614 | 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.