Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22971 | 69136;69137;69138 | chr2:178577424;178577423;178577422 | chr2:179442151;179442150;179442149 |
| N2AB | 21330 | 64213;64214;64215 | chr2:178577424;178577423;178577422 | chr2:179442151;179442150;179442149 |
| N2A | 20403 | 61432;61433;61434 | chr2:178577424;178577423;178577422 | chr2:179442151;179442150;179442149 |
| N2B | 13906 | 41941;41942;41943 | chr2:178577424;178577423;178577422 | chr2:179442151;179442150;179442149 |
| Novex-1 | 14031 | 42316;42317;42318 | chr2:178577424;178577423;178577422 | chr2:179442151;179442150;179442149 |
| Novex-2 | 14098 | 42517;42518;42519 | chr2:178577424;178577423;178577422 | chr2:179442151;179442150;179442149 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/F | rs1335554435  |
-1.431 | 1.0 | N | 0.808 | 0.604 | 0.581565680727 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/F | rs1335554435 |
-1.431 | 1.0 | N | 0.808 | 0.604 | 0.581565680727 | gnomAD-4.0.0 | 3.19523E-06 | None | None | None | None | N | None | 0 | 2.28833E-05 | None | 0 | 0 | None | 0 | 0 | 2.86937E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9575 | likely_pathogenic | 0.9567 | pathogenic | -1.166 | Destabilizing | 0.999 | D | 0.673 | neutral | None | None | None | None | N |
| I/C | 0.9474 | likely_pathogenic | 0.9443 | pathogenic | -1.01 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| I/D | 0.997 | likely_pathogenic | 0.9972 | pathogenic | -0.147 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| I/E | 0.9927 | likely_pathogenic | 0.9925 | pathogenic | -0.177 | Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| I/F | 0.5237 | ambiguous | 0.4995 | ambiguous | -1.037 | Destabilizing | 1.0 | D | 0.808 | deleterious | N | 0.494429372 | None | None | N |
| I/G | 0.9916 | likely_pathogenic | 0.9917 | pathogenic | -1.401 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| I/H | 0.9785 | likely_pathogenic | 0.9759 | pathogenic | -0.734 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| I/K | 0.9761 | likely_pathogenic | 0.9741 | pathogenic | -0.449 | Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| I/L | 0.253 | likely_benign | 0.282 | benign | -0.628 | Destabilizing | 0.993 | D | 0.4 | neutral | D | 0.534235767 | None | None | N |
| I/M | 0.3192 | likely_benign | 0.3329 | benign | -0.613 | Destabilizing | 1.0 | D | 0.785 | deleterious | N | 0.5051343 | None | None | N |
| I/N | 0.9531 | likely_pathogenic | 0.9571 | pathogenic | -0.256 | Destabilizing | 1.0 | D | 0.885 | deleterious | D | 0.535266424 | None | None | N |
| I/P | 0.994 | likely_pathogenic | 0.9939 | pathogenic | -0.776 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| I/Q | 0.9778 | likely_pathogenic | 0.9765 | pathogenic | -0.466 | Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| I/R | 0.9625 | likely_pathogenic | 0.9589 | pathogenic | -0.035 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| I/S | 0.9522 | likely_pathogenic | 0.953 | pathogenic | -0.925 | Destabilizing | 1.0 | D | 0.842 | deleterious | D | 0.532755687 | None | None | N |
| I/T | 0.933 | likely_pathogenic | 0.9283 | pathogenic | -0.841 | Destabilizing | 1.0 | D | 0.787 | deleterious | D | 0.53575592 | None | None | N |
| I/V | 0.1302 | likely_benign | 0.1189 | benign | -0.776 | Destabilizing | 0.993 | D | 0.334 | neutral | N | 0.442679895 | None | None | N |
| I/W | 0.9792 | likely_pathogenic | 0.9765 | pathogenic | -1.009 | Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | N |
| I/Y | 0.9176 | likely_pathogenic | 0.9123 | pathogenic | -0.723 | Destabilizing | 1.0 | D | 0.842 | deleterious | 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.