Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30555 | 91888;91889;91890 | chr2:178550175;178550174;178550173 | chr2:179414902;179414901;179414900 |
| N2AB | 28914 | 86965;86966;86967 | chr2:178550175;178550174;178550173 | chr2:179414902;179414901;179414900 |
| N2A | 27987 | 84184;84185;84186 | chr2:178550175;178550174;178550173 | chr2:179414902;179414901;179414900 |
| N2B | 21490 | 64693;64694;64695 | chr2:178550175;178550174;178550173 | chr2:179414902;179414901;179414900 |
| Novex-1 | 21615 | 65068;65069;65070 | chr2:178550175;178550174;178550173 | chr2:179414902;179414901;179414900 |
| Novex-2 | 21682 | 65269;65270;65271 | chr2:178550175;178550174;178550173 | chr2:179414902;179414901;179414900 |
| 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 | rs1698774986  |
None | 0.822 | N | 0.569 | 0.293 | 0.552940642338 | gnomAD-4.0.0 | 1.36842E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79898E-06 | 0 | 0 |
| V/M | rs771790427 |
-0.301 | 0.942 | N | 0.545 | 0.191 | 0.461671691612 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/M | rs771790427 |
-0.301 | 0.942 | N | 0.545 | 0.191 | 0.461671691612 | gnomAD-4.0.0 | 1.59126E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43279E-05 | 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 | 0.1931 | likely_benign | 0.1876 | benign | -0.564 | Destabilizing | 0.822 | D | 0.569 | neutral | N | 0.40797825 | None | None | I |
| V/C | 0.7402 | likely_pathogenic | 0.7214 | pathogenic | -0.649 | Destabilizing | 0.998 | D | 0.585 | neutral | None | None | None | None | I |
| V/D | 0.5495 | ambiguous | 0.5349 | ambiguous | -0.464 | Destabilizing | 0.993 | D | 0.679 | prob.neutral | None | None | None | None | I |
| V/E | 0.4118 | ambiguous | 0.3956 | ambiguous | -0.572 | Destabilizing | 0.99 | D | 0.648 | neutral | N | 0.424195709 | None | None | I |
| V/F | 0.2213 | likely_benign | 0.219 | benign | -0.757 | Destabilizing | 0.956 | D | 0.566 | neutral | None | None | None | None | I |
| V/G | 0.3224 | likely_benign | 0.3116 | benign | -0.704 | Destabilizing | 0.971 | D | 0.672 | neutral | N | 0.505448868 | None | None | I |
| V/H | 0.643 | likely_pathogenic | 0.62 | pathogenic | -0.266 | Destabilizing | 0.998 | D | 0.697 | prob.neutral | None | None | None | None | I |
| V/I | 0.0761 | likely_benign | 0.0758 | benign | -0.342 | Destabilizing | 0.019 | N | 0.346 | neutral | None | None | None | None | I |
| V/K | 0.4674 | ambiguous | 0.4281 | ambiguous | -0.567 | Destabilizing | 0.978 | D | 0.652 | neutral | None | None | None | None | I |
| V/L | 0.1633 | likely_benign | 0.1565 | benign | -0.342 | Destabilizing | 0.014 | N | 0.341 | neutral | N | 0.414597578 | None | None | I |
| V/M | 0.1435 | likely_benign | 0.1416 | benign | -0.421 | Destabilizing | 0.942 | D | 0.545 | neutral | N | 0.449768944 | None | None | I |
| V/N | 0.3601 | ambiguous | 0.3437 | ambiguous | -0.293 | Destabilizing | 0.993 | D | 0.675 | prob.neutral | None | None | None | None | I |
| V/P | 0.3714 | ambiguous | 0.3335 | benign | -0.382 | Destabilizing | 0.993 | D | 0.647 | neutral | None | None | None | None | I |
| V/Q | 0.3853 | ambiguous | 0.356 | ambiguous | -0.534 | Destabilizing | 0.993 | D | 0.645 | neutral | None | None | None | None | I |
| V/R | 0.4199 | ambiguous | 0.3853 | ambiguous | -0.027 | Destabilizing | 0.978 | D | 0.673 | neutral | None | None | None | None | I |
| V/S | 0.258 | likely_benign | 0.2471 | benign | -0.631 | Destabilizing | 0.978 | D | 0.644 | neutral | None | None | None | None | I |
| V/T | 0.2244 | likely_benign | 0.2207 | benign | -0.639 | Destabilizing | 0.86 | D | 0.551 | neutral | None | None | None | None | I |
| V/W | 0.837 | likely_pathogenic | 0.8374 | pathogenic | -0.84 | Destabilizing | 0.998 | D | 0.71 | prob.delet. | None | None | None | None | I |
| V/Y | 0.5787 | likely_pathogenic | 0.56 | ambiguous | -0.554 | Destabilizing | 0.978 | D | 0.564 | 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.