Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25565 | 76918;76919;76920 | chr2:178569439;178569438;178569437 | chr2:179434166;179434165;179434164 |
| N2AB | 23924 | 71995;71996;71997 | chr2:178569439;178569438;178569437 | chr2:179434166;179434165;179434164 |
| N2A | 22997 | 69214;69215;69216 | chr2:178569439;178569438;178569437 | chr2:179434166;179434165;179434164 |
| N2B | 16500 | 49723;49724;49725 | chr2:178569439;178569438;178569437 | chr2:179434166;179434165;179434164 |
| Novex-1 | 16625 | 50098;50099;50100 | chr2:178569439;178569438;178569437 | chr2:179434166;179434165;179434164 |
| Novex-2 | 16692 | 50299;50300;50301 | chr2:178569439;178569438;178569437 | chr2:179434166;179434165;179434164 |
| 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/P | rs753679035  |
0.262 | 0.999 | D | 0.697 | 0.62 | 0.552367828057 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| S/P | rs753679035 |
0.262 | 0.999 | D | 0.697 | 0.62 | 0.552367828057 | gnomAD-4.0.0 | 8.21342E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.0796E-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 | 0.1015 | likely_benign | 0.1002 | benign | -0.475 | Destabilizing | 0.987 | D | 0.421 | neutral | D | 0.523439983 | None | None | N |
| S/C | 0.1155 | likely_benign | 0.1099 | benign | -0.011 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | N | 0.488938921 | None | None | N |
| S/D | 0.884 | likely_pathogenic | 0.8727 | pathogenic | -1.275 | Destabilizing | 1.0 | D | 0.616 | neutral | None | None | None | None | N |
| S/E | 0.8303 | likely_pathogenic | 0.8175 | pathogenic | -0.997 | Destabilizing | 0.999 | D | 0.57 | neutral | None | None | None | None | N |
| S/F | 0.3242 | likely_benign | 0.2915 | benign | -0.377 | Destabilizing | 0.997 | D | 0.753 | deleterious | N | 0.491799304 | None | None | N |
| S/G | 0.2261 | likely_benign | 0.2254 | benign | -0.917 | Destabilizing | 0.999 | D | 0.447 | neutral | None | None | None | None | N |
| S/H | 0.5989 | likely_pathogenic | 0.5572 | ambiguous | -1.166 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| S/I | 0.3179 | likely_benign | 0.2873 | benign | 0.682 | Stabilizing | 0.995 | D | 0.655 | neutral | None | None | None | None | N |
| S/K | 0.928 | likely_pathogenic | 0.9129 | pathogenic | 0.587 | Stabilizing | 0.999 | D | 0.552 | neutral | None | None | None | None | N |
| S/L | 0.112 | likely_benign | 0.1107 | benign | 0.682 | Stabilizing | 0.269 | N | 0.465 | neutral | None | None | None | None | N |
| S/M | 0.1697 | likely_benign | 0.1692 | benign | 0.352 | Stabilizing | 0.998 | D | 0.723 | prob.delet. | None | None | None | None | N |
| S/N | 0.3561 | ambiguous | 0.3255 | benign | -0.424 | Destabilizing | 1.0 | D | 0.6 | neutral | None | None | None | None | N |
| S/P | 0.9806 | likely_pathogenic | 0.9799 | pathogenic | 0.329 | Stabilizing | 0.999 | D | 0.697 | prob.neutral | D | 0.526539783 | None | None | N |
| S/Q | 0.6833 | likely_pathogenic | 0.6699 | pathogenic | 0.016 | Stabilizing | 1.0 | D | 0.635 | neutral | None | None | None | None | N |
| S/R | 0.9007 | likely_pathogenic | 0.8796 | pathogenic | -0.13 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | N |
| S/T | 0.0999 | likely_benign | 0.1021 | benign | 0.024 | Stabilizing | 0.994 | D | 0.46 | neutral | N | 0.451131594 | None | None | N |
| S/V | 0.2423 | likely_benign | 0.2346 | benign | 0.329 | Stabilizing | 0.983 | D | 0.581 | neutral | None | None | None | None | N |
| S/W | 0.568 | likely_pathogenic | 0.5323 | ambiguous | -0.751 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | N |
| S/Y | 0.2834 | likely_benign | 0.2448 | benign | -0.176 | Destabilizing | 0.999 | D | 0.775 | deleterious | N | 0.508435528 | 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.