Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22867 | 68824;68825;68826 | chr2:178577827;178577826;178577825 | chr2:179442554;179442553;179442552 |
| N2AB | 21226 | 63901;63902;63903 | chr2:178577827;178577826;178577825 | chr2:179442554;179442553;179442552 |
| N2A | 20299 | 61120;61121;61122 | chr2:178577827;178577826;178577825 | chr2:179442554;179442553;179442552 |
| N2B | 13802 | 41629;41630;41631 | chr2:178577827;178577826;178577825 | chr2:179442554;179442553;179442552 |
| Novex-1 | 13927 | 42004;42005;42006 | chr2:178577827;178577826;178577825 | chr2:179442554;179442553;179442552 |
| Novex-2 | 13994 | 42205;42206;42207 | chr2:178577827;178577826;178577825 | chr2:179442554;179442553;179442552 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/F | rs1397080164  |
0.014 | 0.981 | N | 0.531 | 0.247 | 0.411401001288 | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | I | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/F | rs1397080164 |
0.014 | 0.981 | N | 0.531 | 0.247 | 0.411401001288 | gnomAD-4.0.0 | 1.59732E-06 | None | None | None | None | I | None | 5.67988E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/H | rs368484355 |
0.556 | 0.983 | N | 0.595 | 0.372 | None | gnomAD-2.1.1 | 1.08E-05 | None | None | None | None | I | None | 4.14E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.58E-05 | 0 |
| Y/H | rs368484355 |
0.556 | 0.983 | N | 0.595 | 0.372 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| Y/H | rs368484355 |
0.556 | 0.983 | N | 0.595 | 0.372 | None | gnomAD-4.0.0 | 1.86229E-05 | None | None | None | None | I | None | 2.67337E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.37623E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.8268 | likely_pathogenic | 0.8659 | pathogenic | -1.166 | Destabilizing | 0.916 | D | 0.551 | neutral | None | None | None | None | I |
| Y/C | 0.481 | ambiguous | 0.4948 | ambiguous | 0.033 | Stabilizing | 0.999 | D | 0.673 | neutral | N | 0.49782347 | None | None | I |
| Y/D | 0.6536 | likely_pathogenic | 0.7581 | pathogenic | 0.514 | Stabilizing | 0.983 | D | 0.69 | prob.neutral | N | 0.472970225 | None | None | I |
| Y/E | 0.891 | likely_pathogenic | 0.9311 | pathogenic | 0.508 | Stabilizing | 0.975 | D | 0.545 | neutral | None | None | None | None | I |
| Y/F | 0.1667 | likely_benign | 0.2023 | benign | -0.62 | Destabilizing | 0.981 | D | 0.531 | neutral | N | 0.468913986 | None | None | I |
| Y/G | 0.6669 | likely_pathogenic | 0.7101 | pathogenic | -1.394 | Destabilizing | 0.975 | D | 0.602 | neutral | None | None | None | None | I |
| Y/H | 0.4317 | ambiguous | 0.5024 | ambiguous | -0.177 | Destabilizing | 0.983 | D | 0.595 | neutral | N | 0.476090675 | None | None | I |
| Y/I | 0.8496 | likely_pathogenic | 0.8975 | pathogenic | -0.559 | Destabilizing | 0.987 | D | 0.63 | neutral | None | None | None | None | I |
| Y/K | 0.8439 | likely_pathogenic | 0.8859 | pathogenic | -0.075 | Destabilizing | 0.845 | D | 0.531 | neutral | None | None | None | None | I |
| Y/L | 0.789 | likely_pathogenic | 0.8398 | pathogenic | -0.559 | Destabilizing | 0.916 | D | 0.607 | neutral | None | None | None | None | I |
| Y/M | 0.8301 | likely_pathogenic | 0.8715 | pathogenic | -0.217 | Destabilizing | 0.999 | D | 0.595 | neutral | None | None | None | None | I |
| Y/N | 0.284 | likely_benign | 0.3014 | benign | -0.197 | Destabilizing | 0.967 | D | 0.659 | neutral | N | 0.467508477 | None | None | I |
| Y/P | 0.9895 | likely_pathogenic | 0.9924 | pathogenic | -0.744 | Destabilizing | 0.996 | D | 0.697 | prob.neutral | None | None | None | None | I |
| Y/Q | 0.819 | likely_pathogenic | 0.859 | pathogenic | -0.205 | Destabilizing | 0.975 | D | 0.629 | neutral | None | None | None | None | I |
| Y/R | 0.7161 | likely_pathogenic | 0.7648 | pathogenic | 0.302 | Stabilizing | 0.073 | N | 0.395 | neutral | None | None | None | None | I |
| Y/S | 0.5361 | ambiguous | 0.6195 | pathogenic | -0.666 | Destabilizing | 0.967 | D | 0.563 | neutral | N | 0.478013472 | None | None | I |
| Y/T | 0.7808 | likely_pathogenic | 0.8316 | pathogenic | -0.581 | Destabilizing | 0.975 | D | 0.617 | neutral | None | None | None | None | I |
| Y/V | 0.7623 | likely_pathogenic | 0.8115 | pathogenic | -0.744 | Destabilizing | 0.987 | D | 0.563 | neutral | None | None | None | None | I |
| Y/W | 0.6389 | likely_pathogenic | 0.7049 | pathogenic | -0.603 | Destabilizing | 0.999 | D | 0.571 | 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.