Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26886 | 80881;80882;80883 | chr2:178565476;178565475;178565474 | chr2:179430203;179430202;179430201 |
| N2AB | 25245 | 75958;75959;75960 | chr2:178565476;178565475;178565474 | chr2:179430203;179430202;179430201 |
| N2A | 24318 | 73177;73178;73179 | chr2:178565476;178565475;178565474 | chr2:179430203;179430202;179430201 |
| N2B | 17821 | 53686;53687;53688 | chr2:178565476;178565475;178565474 | chr2:179430203;179430202;179430201 |
| Novex-1 | 17946 | 54061;54062;54063 | chr2:178565476;178565475;178565474 | chr2:179430203;179430202;179430201 |
| Novex-2 | 18013 | 54262;54263;54264 | chr2:178565476;178565475;178565474 | chr2:179430203;179430202;179430201 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs1373580464  |
-0.428 | 0.999 | N | 0.505 | 0.491 | 0.128392430309 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 2.58565E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| F/L | rs1373580464 |
-0.428 | 0.999 | N | 0.505 | 0.491 | 0.128392430309 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 1.20651E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| F/L | rs1373580464 |
-0.428 | 0.999 | N | 0.505 | 0.491 | 0.128392430309 | gnomAD-4.0.0 | 4.95921E-06 | None | None | None | None | I | None | 1.06883E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.746 | likely_pathogenic | 0.7929 | pathogenic | -1.29 | Destabilizing | 1.0 | D | 0.592 | neutral | None | None | None | None | I |
| F/C | 0.5661 | likely_pathogenic | 0.6581 | pathogenic | -0.775 | Destabilizing | 1.0 | D | 0.646 | neutral | N | 0.483658191 | None | None | I |
| F/D | 0.9208 | likely_pathogenic | 0.9434 | pathogenic | 0.027 | Stabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | I |
| F/E | 0.9277 | likely_pathogenic | 0.9459 | pathogenic | 0.05 | Stabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | I |
| F/G | 0.8192 | likely_pathogenic | 0.841 | pathogenic | -1.504 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | I |
| F/H | 0.776 | likely_pathogenic | 0.8212 | pathogenic | 0.062 | Stabilizing | 1.0 | D | 0.623 | neutral | None | None | None | None | I |
| F/I | 0.5259 | ambiguous | 0.5881 | pathogenic | -0.698 | Destabilizing | 1.0 | D | 0.637 | neutral | N | 0.490376976 | None | None | I |
| F/K | 0.9345 | likely_pathogenic | 0.9521 | pathogenic | -0.605 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | I |
| F/L | 0.9201 | likely_pathogenic | 0.9324 | pathogenic | -0.698 | Destabilizing | 0.999 | D | 0.505 | neutral | N | 0.444369753 | None | None | I |
| F/M | 0.6964 | likely_pathogenic | 0.734 | pathogenic | -0.769 | Destabilizing | 1.0 | D | 0.668 | neutral | None | None | None | None | I |
| F/N | 0.8469 | likely_pathogenic | 0.8807 | pathogenic | -0.755 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | I |
| F/P | 0.9883 | likely_pathogenic | 0.9883 | pathogenic | -0.883 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| F/Q | 0.8675 | likely_pathogenic | 0.8913 | pathogenic | -0.754 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | I |
| F/R | 0.8673 | likely_pathogenic | 0.8902 | pathogenic | -0.142 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | None | None | None | None | I |
| F/S | 0.6503 | likely_pathogenic | 0.7054 | pathogenic | -1.363 | Destabilizing | 1.0 | D | 0.624 | neutral | N | 0.463499806 | None | None | I |
| F/T | 0.8005 | likely_pathogenic | 0.8454 | pathogenic | -1.245 | Destabilizing | 1.0 | D | 0.621 | neutral | None | None | None | None | I |
| F/V | 0.4253 | ambiguous | 0.4945 | ambiguous | -0.883 | Destabilizing | 1.0 | D | 0.597 | neutral | N | 0.49584151 | None | None | I |
| F/W | 0.6626 | likely_pathogenic | 0.6871 | pathogenic | -0.322 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | I |
| F/Y | 0.2589 | likely_benign | 0.3237 | benign | -0.432 | Destabilizing | 0.999 | D | 0.551 | neutral | N | 0.505866503 | 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.