Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29969 | 90130;90131;90132 | chr2:178552995;178552994;178552993 | chr2:179417722;179417721;179417720 |
| N2AB | 28328 | 85207;85208;85209 | chr2:178552995;178552994;178552993 | chr2:179417722;179417721;179417720 |
| N2A | 27401 | 82426;82427;82428 | chr2:178552995;178552994;178552993 | chr2:179417722;179417721;179417720 |
| N2B | 20904 | 62935;62936;62937 | chr2:178552995;178552994;178552993 | chr2:179417722;179417721;179417720 |
| Novex-1 | 21029 | 63310;63311;63312 | chr2:178552995;178552994;178552993 | chr2:179417722;179417721;179417720 |
| Novex-2 | 21096 | 63511;63512;63513 | chr2:178552995;178552994;178552993 | chr2:179417722;179417721;179417720 |
| 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 | rs201220828  |
-2.696 | 0.104 | N | 0.617 | 0.226 | None | gnomAD-2.1.1 | 1.44E-05 | None | None | None | None | N | None | 1.6544E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs201220828 |
-2.696 | 0.104 | N | 0.617 | 0.226 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 1.20627E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs201220828 |
-2.696 | 0.104 | N | 0.617 | 0.226 | None | gnomAD-4.0.0 | 5.58327E-06 | None | None | None | None | N | None | 9.34255E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.20297E-05 |
| V/I | None | None | None | N | 0.236 | 0.069 | 0.262662153117 | gnomAD-4.0.0 | 1.59595E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85829E-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 | 0.4703 | ambiguous | 0.3805 | ambiguous | -2.451 | Highly Destabilizing | 0.104 | N | 0.617 | neutral | N | 0.470101337 | None | None | N |
| V/C | 0.7273 | likely_pathogenic | 0.6311 | pathogenic | -2.018 | Highly Destabilizing | 0.968 | D | 0.699 | prob.neutral | None | None | None | None | N |
| V/D | 0.7652 | likely_pathogenic | 0.6886 | pathogenic | -3.314 | Highly Destabilizing | 0.667 | D | 0.774 | deleterious | N | 0.469847847 | None | None | N |
| V/E | 0.5942 | likely_pathogenic | 0.5335 | ambiguous | -3.115 | Highly Destabilizing | 0.726 | D | 0.702 | prob.neutral | None | None | None | None | N |
| V/F | 0.2712 | likely_benign | 0.2051 | benign | -1.399 | Destabilizing | 0.497 | N | 0.697 | prob.neutral | N | 0.467494444 | None | None | N |
| V/G | 0.5943 | likely_pathogenic | 0.5078 | ambiguous | -2.95 | Highly Destabilizing | 0.667 | D | 0.745 | deleterious | N | 0.49424598 | None | None | N |
| V/H | 0.6339 | likely_pathogenic | 0.5372 | ambiguous | -2.612 | Highly Destabilizing | 0.968 | D | 0.769 | deleterious | None | None | None | None | N |
| V/I | 0.0664 | likely_benign | 0.0597 | benign | -1.044 | Destabilizing | None | N | 0.236 | neutral | N | 0.379625707 | None | None | N |
| V/K | 0.5162 | ambiguous | 0.4388 | ambiguous | -2.114 | Highly Destabilizing | 0.726 | D | 0.702 | prob.neutral | None | None | None | None | N |
| V/L | 0.2185 | likely_benign | 0.1586 | benign | -1.044 | Destabilizing | 0.009 | N | 0.443 | neutral | N | 0.45489147 | None | None | N |
| V/M | 0.1939 | likely_benign | 0.1491 | benign | -1.113 | Destabilizing | 0.567 | D | 0.701 | prob.neutral | None | None | None | None | N |
| V/N | 0.5125 | ambiguous | 0.3725 | ambiguous | -2.426 | Highly Destabilizing | 0.89 | D | 0.795 | deleterious | None | None | None | None | N |
| V/P | 0.9862 | likely_pathogenic | 0.9765 | pathogenic | -1.49 | Destabilizing | 0.89 | D | 0.704 | prob.neutral | None | None | None | None | N |
| V/Q | 0.5055 | ambiguous | 0.4358 | ambiguous | -2.298 | Highly Destabilizing | 0.89 | D | 0.719 | prob.delet. | None | None | None | None | N |
| V/R | 0.4281 | ambiguous | 0.3534 | ambiguous | -1.814 | Destabilizing | 0.726 | D | 0.796 | deleterious | None | None | None | None | N |
| V/S | 0.5055 | ambiguous | 0.3842 | ambiguous | -2.971 | Highly Destabilizing | 0.726 | D | 0.678 | prob.neutral | None | None | None | None | N |
| V/T | 0.355 | ambiguous | 0.2679 | benign | -2.652 | Highly Destabilizing | 0.272 | N | 0.657 | neutral | None | None | None | None | N |
| V/W | 0.8663 | likely_pathogenic | 0.8104 | pathogenic | -1.954 | Destabilizing | 0.968 | D | 0.734 | prob.delet. | None | None | None | None | N |
| V/Y | 0.6341 | likely_pathogenic | 0.5382 | ambiguous | -1.68 | Destabilizing | 0.726 | D | 0.707 | prob.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.