Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25496 | 76711;76712;76713 | chr2:178569646;178569645;178569644 | chr2:179434373;179434372;179434371 |
| N2AB | 23855 | 71788;71789;71790 | chr2:178569646;178569645;178569644 | chr2:179434373;179434372;179434371 |
| N2A | 22928 | 69007;69008;69009 | chr2:178569646;178569645;178569644 | chr2:179434373;179434372;179434371 |
| N2B | 16431 | 49516;49517;49518 | chr2:178569646;178569645;178569644 | chr2:179434373;179434372;179434371 |
| Novex-1 | 16556 | 49891;49892;49893 | chr2:178569646;178569645;178569644 | chr2:179434373;179434372;179434371 |
| Novex-2 | 16623 | 50092;50093;50094 | chr2:178569646;178569645;178569644 | chr2:179434373;179434372;179434371 |
| 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/R | rs886039105  |
0.15 | 1.0 | N | 0.673 | 0.419 | None | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 1.14758E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/R | rs886039105 |
0.15 | 1.0 | N | 0.673 | 0.419 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/R | rs886039105 |
0.15 | 1.0 | N | 0.673 | 0.419 | None | gnomAD-4.0.0 | 1.31555E-05 | None | None | None | None | I | None | 4.82835E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.0831 | likely_benign | 0.0813 | benign | -0.354 | Destabilizing | 0.999 | D | 0.781 | deleterious | N | 0.516332292 | None | None | I |
| P/C | 0.4121 | ambiguous | 0.4308 | ambiguous | -0.591 | Destabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | I |
| P/D | 0.4106 | ambiguous | 0.3951 | ambiguous | -0.489 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | I |
| P/E | 0.2851 | likely_benign | 0.2797 | benign | -0.603 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | I |
| P/F | 0.4044 | ambiguous | 0.4127 | ambiguous | -0.684 | Destabilizing | 1.0 | D | 0.663 | prob.neutral | None | None | None | None | I |
| P/G | 0.2929 | likely_benign | 0.286 | benign | -0.454 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | I |
| P/H | 0.1877 | likely_benign | 0.1882 | benign | -0.096 | Destabilizing | 1.0 | D | 0.629 | neutral | N | 0.491080699 | None | None | I |
| P/I | 0.2546 | likely_benign | 0.2668 | benign | -0.236 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | I |
| P/K | 0.255 | likely_benign | 0.2666 | benign | -0.439 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | I |
| P/L | 0.1083 | likely_benign | 0.1118 | benign | -0.236 | Destabilizing | 1.0 | D | 0.725 | deleterious | N | 0.483990354 | None | None | I |
| P/M | 0.2504 | likely_benign | 0.2608 | benign | -0.446 | Destabilizing | 1.0 | D | 0.628 | neutral | None | None | None | None | I |
| P/N | 0.2854 | likely_benign | 0.2885 | benign | -0.158 | Destabilizing | 1.0 | D | 0.697 | prob.delet. | None | None | None | None | I |
| P/Q | 0.1542 | likely_benign | 0.1602 | benign | -0.393 | Destabilizing | 1.0 | D | 0.737 | deleterious | None | None | None | None | I |
| P/R | 0.2033 | likely_benign | 0.1974 | benign | 0.041 | Stabilizing | 1.0 | D | 0.673 | prob.neutral | N | 0.483572281 | None | None | I |
| P/S | 0.1221 | likely_benign | 0.1225 | benign | -0.431 | Destabilizing | 1.0 | D | 0.806 | deleterious | N | 0.466943621 | None | None | I |
| P/T | 0.0966 | likely_benign | 0.099 | benign | -0.453 | Destabilizing | 1.0 | D | 0.793 | deleterious | N | 0.47467767 | None | None | I |
| P/V | 0.184 | likely_benign | 0.1863 | benign | -0.244 | Destabilizing | 1.0 | D | 0.732 | deleterious | None | None | None | None | I |
| P/W | 0.6127 | likely_pathogenic | 0.601 | pathogenic | -0.778 | Destabilizing | 1.0 | D | 0.565 | neutral | None | None | None | None | I |
| P/Y | 0.4173 | ambiguous | 0.4232 | ambiguous | -0.478 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | 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.