Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16909 | 50950;50951;50952 | chr2:178611504;178611503;178611502 | chr2:179476231;179476230;179476229 |
| N2AB | 15268 | 46027;46028;46029 | chr2:178611504;178611503;178611502 | chr2:179476231;179476230;179476229 |
| N2A | 14341 | 43246;43247;43248 | chr2:178611504;178611503;178611502 | chr2:179476231;179476230;179476229 |
| N2B | 7844 | 23755;23756;23757 | chr2:178611504;178611503;178611502 | chr2:179476231;179476230;179476229 |
| Novex-1 | 7969 | 24130;24131;24132 | chr2:178611504;178611503;178611502 | chr2:179476231;179476230;179476229 |
| Novex-2 | 8036 | 24331;24332;24333 | chr2:178611504;178611503;178611502 | chr2:179476231;179476230;179476229 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | None | None | 0.198 | N | 0.217 | 0.064 | 0.1749357433 | gnomAD-4.0.0 | 1.59293E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86149E-06 | 0 | 0 |
| D/H | rs2056319066  |
None | 1.0 | N | 0.681 | 0.359 | 0.350524144436 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 2.88184E-04 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/H | rs2056319066 |
None | 1.0 | N | 0.681 | 0.359 | 0.350524144436 | gnomAD-4.0.0 | 3.84757E-06 | None | None | None | None | I | None | 0 | 0 | None | 1.2278E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2817 | likely_benign | 0.3917 | ambiguous | 0.149 | Stabilizing | 0.978 | D | 0.585 | neutral | N | 0.440172983 | None | None | I |
| D/C | 0.7914 | likely_pathogenic | 0.8889 | pathogenic | -0.255 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| D/E | 0.1607 | likely_benign | 0.202 | benign | -0.389 | Destabilizing | 0.198 | N | 0.217 | neutral | N | 0.375372356 | None | None | I |
| D/F | 0.7589 | likely_pathogenic | 0.8562 | pathogenic | 0.648 | Stabilizing | 0.999 | D | 0.727 | prob.delet. | None | None | None | None | I |
| D/G | 0.2865 | likely_benign | 0.3604 | ambiguous | -0.124 | Destabilizing | 0.989 | D | 0.617 | neutral | N | 0.4360119 | None | None | I |
| D/H | 0.5304 | ambiguous | 0.6589 | pathogenic | 1.053 | Stabilizing | 1.0 | D | 0.681 | prob.neutral | N | 0.471597352 | None | None | I |
| D/I | 0.5639 | ambiguous | 0.732 | pathogenic | 0.844 | Stabilizing | 0.999 | D | 0.741 | deleterious | None | None | None | None | I |
| D/K | 0.6521 | likely_pathogenic | 0.7799 | pathogenic | 0.358 | Stabilizing | 0.983 | D | 0.58 | neutral | None | None | None | None | I |
| D/L | 0.5713 | likely_pathogenic | 0.7175 | pathogenic | 0.844 | Stabilizing | 0.998 | D | 0.731 | prob.delet. | None | None | None | None | I |
| D/M | 0.7374 | likely_pathogenic | 0.8522 | pathogenic | 0.582 | Stabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | I |
| D/N | 0.1854 | likely_benign | 0.2335 | benign | -0.348 | Destabilizing | 0.989 | D | 0.537 | neutral | N | 0.458736122 | None | None | I |
| D/P | 0.8902 | likely_pathogenic | 0.9295 | pathogenic | 0.636 | Stabilizing | 0.999 | D | 0.688 | prob.neutral | None | None | None | None | I |
| D/Q | 0.502 | ambiguous | 0.6581 | pathogenic | -0.209 | Destabilizing | 0.995 | D | 0.548 | neutral | None | None | None | None | I |
| D/R | 0.7088 | likely_pathogenic | 0.8211 | pathogenic | 0.748 | Stabilizing | 0.995 | D | 0.721 | prob.delet. | None | None | None | None | I |
| D/S | 0.2488 | likely_benign | 0.3153 | benign | -0.463 | Destabilizing | 0.983 | D | 0.489 | neutral | None | None | None | None | I |
| D/T | 0.3723 | ambiguous | 0.5081 | ambiguous | -0.21 | Destabilizing | 0.998 | D | 0.63 | neutral | None | None | None | None | I |
| D/V | 0.3389 | likely_benign | 0.4876 | ambiguous | 0.636 | Stabilizing | 0.997 | D | 0.711 | prob.delet. | N | 0.460652906 | None | None | I |
| D/W | 0.9433 | likely_pathogenic | 0.9762 | pathogenic | 0.796 | Stabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | I |
| D/Y | 0.3952 | ambiguous | 0.5297 | ambiguous | 0.925 | Stabilizing | 0.999 | D | 0.727 | prob.delet. | N | 0.480047153 | 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.