Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19887 | 59884;59885;59886 | chr2:178592245;178592244;178592243 | chr2:179456972;179456971;179456970 |
| N2AB | 18246 | 54961;54962;54963 | chr2:178592245;178592244;178592243 | chr2:179456972;179456971;179456970 |
| N2A | 17319 | 52180;52181;52182 | chr2:178592245;178592244;178592243 | chr2:179456972;179456971;179456970 |
| N2B | 10822 | 32689;32690;32691 | chr2:178592245;178592244;178592243 | chr2:179456972;179456971;179456970 |
| Novex-1 | 10947 | 33064;33065;33066 | chr2:178592245;178592244;178592243 | chr2:179456972;179456971;179456970 |
| Novex-2 | 11014 | 33265;33266;33267 | chr2:178592245;178592244;178592243 | chr2:179456972;179456971;179456970 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/I | None | None | 1.0 | N | 0.805 | 0.406 | 0.572589462766 | gnomAD-4.0.0 | 1.5964E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 2.41779E-04 | 0 | 0 | 0 |
| S/R | rs748248730  |
-0.18 | 1.0 | N | 0.811 | 0.334 | 0.433713641954 | gnomAD-2.1.1 | 8.2E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.11E-06 | 1.68634E-04 |
| S/R | rs748248730 |
-0.18 | 1.0 | N | 0.811 | 0.334 | 0.433713641954 | gnomAD-4.0.0 | 1.64429E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.16026E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0972 | likely_benign | 0.1162 | benign | -0.583 | Destabilizing | 0.998 | D | 0.408 | neutral | None | None | None | None | N |
| S/C | 0.1522 | likely_benign | 0.1874 | benign | -0.36 | Destabilizing | 1.0 | D | 0.779 | deleterious | N | 0.482946262 | None | None | N |
| S/D | 0.6351 | likely_pathogenic | 0.7142 | pathogenic | 0.305 | Stabilizing | 0.999 | D | 0.619 | neutral | None | None | None | None | N |
| S/E | 0.6665 | likely_pathogenic | 0.7469 | pathogenic | 0.286 | Stabilizing | 0.999 | D | 0.613 | neutral | None | None | None | None | N |
| S/F | 0.3134 | likely_benign | 0.3944 | ambiguous | -0.853 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| S/G | 0.1199 | likely_benign | 0.1424 | benign | -0.804 | Destabilizing | 0.999 | D | 0.531 | neutral | N | 0.484414292 | None | None | N |
| S/H | 0.4306 | ambiguous | 0.5286 | ambiguous | -1.196 | Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | N |
| S/I | 0.2854 | likely_benign | 0.3879 | ambiguous | -0.113 | Destabilizing | 1.0 | D | 0.805 | deleterious | N | 0.477626663 | None | None | N |
| S/K | 0.6514 | likely_pathogenic | 0.7649 | pathogenic | -0.478 | Destabilizing | 0.999 | D | 0.611 | neutral | None | None | None | None | N |
| S/L | 0.138 | likely_benign | 0.1736 | benign | -0.113 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | N |
| S/M | 0.2178 | likely_benign | 0.2751 | benign | -0.004 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| S/N | 0.2157 | likely_benign | 0.2854 | benign | -0.383 | Destabilizing | 0.999 | D | 0.584 | neutral | N | 0.483907313 | None | None | N |
| S/P | 0.9083 | likely_pathogenic | 0.9307 | pathogenic | -0.236 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| S/Q | 0.543 | ambiguous | 0.6363 | pathogenic | -0.492 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| S/R | 0.6076 | likely_pathogenic | 0.7261 | pathogenic | -0.386 | Destabilizing | 1.0 | D | 0.811 | deleterious | N | 0.476145406 | None | None | N |
| S/T | 0.0749 | likely_benign | 0.0889 | benign | -0.448 | Destabilizing | 0.999 | D | 0.501 | neutral | N | 0.451256519 | None | None | N |
| S/V | 0.2416 | likely_benign | 0.3149 | benign | -0.236 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | N |
| S/W | 0.5025 | ambiguous | 0.5787 | pathogenic | -0.847 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| S/Y | 0.3031 | likely_benign | 0.3807 | ambiguous | -0.566 | Destabilizing | 1.0 | D | 0.828 | 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.