Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25235 | 75928;75929;75930 | chr2:178570429;178570428;178570427 | chr2:179435156;179435155;179435154 |
| N2AB | 23594 | 71005;71006;71007 | chr2:178570429;178570428;178570427 | chr2:179435156;179435155;179435154 |
| N2A | 22667 | 68224;68225;68226 | chr2:178570429;178570428;178570427 | chr2:179435156;179435155;179435154 |
| N2B | 16170 | 48733;48734;48735 | chr2:178570429;178570428;178570427 | chr2:179435156;179435155;179435154 |
| Novex-1 | 16295 | 49108;49109;49110 | chr2:178570429;178570428;178570427 | chr2:179435156;179435155;179435154 |
| Novex-2 | 16362 | 49309;49310;49311 | chr2:178570429;178570428;178570427 | chr2:179435156;179435155;179435154 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/R | rs372834784  |
-0.67 | 0.997 | N | 0.744 | 0.365 | 0.242244723065 | gnomAD-2.1.1 | 3.59E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 1.20154E-04 | 5.51E-05 | 0 |
| S/R | rs372834784 |
-0.67 | 0.997 | N | 0.744 | 0.365 | 0.242244723065 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 5.89E-05 | 0 | 0 |
| S/R | rs372834784 |
-0.67 | 0.997 | N | 0.744 | 0.365 | 0.242244723065 | gnomAD-4.0.0 | 1.11591E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 9.3882E-05 | 0 | 1.01733E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0966 | likely_benign | 0.099 | benign | -0.797 | Destabilizing | 0.437 | N | 0.435 | neutral | None | None | None | None | I |
| S/C | 0.0832 | likely_benign | 0.0972 | benign | -0.481 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | N | 0.505939153 | None | None | I |
| S/D | 0.8143 | likely_pathogenic | 0.8018 | pathogenic | -0.348 | Destabilizing | 0.992 | D | 0.707 | prob.neutral | None | None | None | None | I |
| S/E | 0.8989 | likely_pathogenic | 0.9055 | pathogenic | -0.355 | Destabilizing | 0.992 | D | 0.683 | prob.neutral | None | None | None | None | I |
| S/F | 0.5013 | ambiguous | 0.5457 | ambiguous | -0.99 | Destabilizing | 0.999 | D | 0.754 | deleterious | None | None | None | None | I |
| S/G | 0.184 | likely_benign | 0.1704 | benign | -1.044 | Destabilizing | 0.956 | D | 0.61 | neutral | N | 0.470489276 | None | None | I |
| S/H | 0.712 | likely_pathogenic | 0.734 | pathogenic | -1.538 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| S/I | 0.6368 | likely_pathogenic | 0.6324 | pathogenic | -0.245 | Destabilizing | 0.997 | D | 0.759 | deleterious | N | 0.490691262 | None | None | I |
| S/K | 0.9653 | likely_pathogenic | 0.9679 | pathogenic | -0.813 | Destabilizing | 0.983 | D | 0.693 | prob.neutral | None | None | None | None | I |
| S/L | 0.2579 | likely_benign | 0.2571 | benign | -0.245 | Destabilizing | 0.983 | D | 0.697 | prob.neutral | None | None | None | None | I |
| S/M | 0.3989 | ambiguous | 0.4199 | ambiguous | 0.103 | Stabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | I |
| S/N | 0.4236 | ambiguous | 0.3845 | ambiguous | -0.742 | Destabilizing | 0.999 | D | 0.741 | deleterious | N | 0.472093254 | None | None | I |
| S/P | 0.9856 | likely_pathogenic | 0.9852 | pathogenic | -0.395 | Destabilizing | 0.998 | D | 0.743 | deleterious | None | None | None | None | I |
| S/Q | 0.8392 | likely_pathogenic | 0.8503 | pathogenic | -0.894 | Destabilizing | 0.999 | D | 0.741 | deleterious | None | None | None | None | I |
| S/R | 0.935 | likely_pathogenic | 0.939 | pathogenic | -0.693 | Destabilizing | 0.997 | D | 0.744 | deleterious | N | 0.521732538 | None | None | I |
| S/T | 0.2241 | likely_benign | 0.2054 | benign | -0.748 | Destabilizing | 0.978 | D | 0.62 | neutral | N | 0.470687676 | None | None | I |
| S/V | 0.5008 | ambiguous | 0.5176 | ambiguous | -0.395 | Destabilizing | 0.995 | D | 0.74 | deleterious | None | None | None | None | I |
| S/W | 0.6787 | likely_pathogenic | 0.7401 | pathogenic | -0.966 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | I |
| S/Y | 0.4825 | ambiguous | 0.5419 | ambiguous | -0.718 | Destabilizing | 0.999 | D | 0.753 | deleterious | 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.