Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22288 | 67087;67088;67089 | chr2:178580517;178580516;178580515 | chr2:179445244;179445243;179445242 |
| N2AB | 20647 | 62164;62165;62166 | chr2:178580517;178580516;178580515 | chr2:179445244;179445243;179445242 |
| N2A | 19720 | 59383;59384;59385 | chr2:178580517;178580516;178580515 | chr2:179445244;179445243;179445242 |
| N2B | 13223 | 39892;39893;39894 | chr2:178580517;178580516;178580515 | chr2:179445244;179445243;179445242 |
| Novex-1 | 13348 | 40267;40268;40269 | chr2:178580517;178580516;178580515 | chr2:179445244;179445243;179445242 |
| Novex-2 | 13415 | 40468;40469;40470 | chr2:178580517;178580516;178580515 | chr2:179445244;179445243;179445242 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs367665060  |
-0.036 | 1.0 | N | 0.765 | 0.511 | None | gnomAD-2.1.1 | 2.87E-05 | None | None | None | None | I | None | 1.65536E-04 | 0 | None | 0 | 0 | None | 0 | None | 4.01E-05 | 2.35E-05 | 0 |
| R/C | rs367665060 |
-0.036 | 1.0 | N | 0.765 | 0.511 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | I | None | 1.4483E-04 | 0 | 0 | 0 | 0 | None | 1.88857E-04 | 0 | 0 | 0 | 0 |
| R/C | rs367665060 |
-0.036 | 1.0 | N | 0.765 | 0.511 | None | gnomAD-4.0.0 | 2.17031E-05 | None | None | None | None | I | None | 1.3359E-04 | 0 | None | 0 | 2.23984E-05 | None | 3.12842E-05 | 0 | 1.69591E-05 | 0 | 3.20554E-05 |
| R/H | rs537871205 |
-1.085 | 1.0 | N | 0.741 | 0.464 | 0.454426139905 | gnomAD-2.1.1 | 2.15E-05 | None | None | None | None | I | None | 4.14E-05 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 4.01E-05 | 7.85E-06 | 1.41203E-04 |
| R/H | rs537871205 |
-1.085 | 1.0 | N | 0.741 | 0.464 | 0.454426139905 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 4.83E-05 | 6.56E-05 | 0 | 0 | 0 | None | 9.43E-05 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs537871205 |
-1.085 | 1.0 | N | 0.741 | 0.464 | 0.454426139905 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/H | rs537871205 |
-1.085 | 1.0 | N | 0.741 | 0.464 | 0.454426139905 | gnomAD-4.0.0 | 1.17806E-05 | None | None | None | None | I | None | 4.00128E-05 | 1.66817E-05 | None | 0 | 2.24054E-05 | None | 1.56377E-05 | 0 | 8.47945E-06 | 2.19684E-05 | 1.6021E-05 |
| R/S | None | None | 1.0 | D | 0.68 | 0.428 | 0.393159880135 | gnomAD-4.0.0 | 1.36923E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31965E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9887 | likely_pathogenic | 0.9888 | pathogenic | 0.078 | Stabilizing | 0.999 | D | 0.583 | neutral | None | None | None | None | I |
| R/C | 0.772 | likely_pathogenic | 0.7903 | pathogenic | -0.244 | Destabilizing | 1.0 | D | 0.765 | deleterious | N | 0.509419352 | None | None | I |
| R/D | 0.996 | likely_pathogenic | 0.9955 | pathogenic | -0.371 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| R/E | 0.9732 | likely_pathogenic | 0.9713 | pathogenic | -0.336 | Destabilizing | 0.999 | D | 0.653 | neutral | None | None | None | None | I |
| R/F | 0.9698 | likely_pathogenic | 0.9715 | pathogenic | -0.275 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | I |
| R/G | 0.9866 | likely_pathogenic | 0.986 | pathogenic | -0.042 | Destabilizing | 1.0 | D | 0.671 | neutral | N | 0.520686752 | None | None | I |
| R/H | 0.547 | ambiguous | 0.5207 | ambiguous | -0.597 | Destabilizing | 1.0 | D | 0.741 | deleterious | N | 0.520706322 | None | None | I |
| R/I | 0.8901 | likely_pathogenic | 0.8933 | pathogenic | 0.349 | Stabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | I |
| R/K | 0.4709 | ambiguous | 0.44 | ambiguous | -0.167 | Destabilizing | 0.998 | D | 0.462 | neutral | None | None | None | None | I |
| R/L | 0.918 | likely_pathogenic | 0.9195 | pathogenic | 0.349 | Stabilizing | 1.0 | D | 0.671 | neutral | N | 0.485946273 | None | None | I |
| R/M | 0.9515 | likely_pathogenic | 0.9529 | pathogenic | -0.116 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | I |
| R/N | 0.9821 | likely_pathogenic | 0.9793 | pathogenic | -0.114 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | I |
| R/P | 0.9986 | likely_pathogenic | 0.9985 | pathogenic | 0.275 | Stabilizing | 1.0 | D | 0.728 | prob.delet. | N | 0.520940242 | None | None | I |
| R/Q | 0.6256 | likely_pathogenic | 0.6076 | pathogenic | -0.119 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | I |
| R/S | 0.9861 | likely_pathogenic | 0.9859 | pathogenic | -0.217 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | D | 0.522378404 | None | None | I |
| R/T | 0.9717 | likely_pathogenic | 0.9723 | pathogenic | -0.086 | Destabilizing | 1.0 | D | 0.672 | neutral | None | None | None | None | I |
| R/V | 0.9375 | likely_pathogenic | 0.9405 | pathogenic | 0.275 | Stabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | I |
| R/W | 0.8024 | likely_pathogenic | 0.8069 | pathogenic | -0.512 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | I |
| R/Y | 0.8966 | likely_pathogenic | 0.9 | pathogenic | -0.107 | Destabilizing | 1.0 | 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.