Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8706 | 26341;26342;26343 | chr2:178715070;178715069;178715068 | chr2:179579797;179579796;179579795 |
| N2AB | 8389 | 25390;25391;25392 | chr2:178715070;178715069;178715068 | chr2:179579797;179579796;179579795 |
| N2A | 7462 | 22609;22610;22611 | chr2:178715070;178715069;178715068 | chr2:179579797;179579796;179579795 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/N | rs377074955  |
-0.121 | 0.785 | N | 0.479 | 0.201 | None | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.56E-05 | None | 0 | None | 0 | 3.56E-05 | 0 |
| D/N | rs377074955 |
-0.121 | 0.785 | N | 0.479 | 0.201 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/N | rs377074955 |
-0.121 | 0.785 | N | 0.479 | 0.201 | None | gnomAD-4.0.0 | 3.9665E-05 | None | None | None | None | N | None | 1.33536E-05 | 0 | None | 0 | 1.55985E-04 | None | 0 | 0 | 4.66239E-05 | 0 | 1.60097E-05 |
| D/V | rs763090296 |
0.298 | 0.865 | N | 0.603 | 0.376 | 0.461144880706 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 3.31455E-04 |
| D/V | rs763090296 |
0.298 | 0.865 | N | 0.603 | 0.376 | 0.461144880706 | gnomAD-4.0.0 | 3.18302E-06 | None | None | None | None | N | None | 0 | 4.57289E-05 | None | 0 | 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 | 0.1238 | likely_benign | 0.1665 | benign | -0.338 | Destabilizing | 0.593 | D | 0.519 | neutral | N | 0.502773923 | None | None | N |
| D/C | 0.5347 | ambiguous | 0.6509 | pathogenic | 0.016 | Stabilizing | 0.989 | D | 0.733 | prob.delet. | None | None | None | None | N |
| D/E | 0.1124 | likely_benign | 0.1114 | benign | -0.503 | Destabilizing | None | N | 0.161 | neutral | N | 0.410805124 | None | None | N |
| D/F | 0.4882 | ambiguous | 0.601 | pathogenic | -0.247 | Destabilizing | 0.99 | D | 0.689 | prob.neutral | None | None | None | None | N |
| D/G | 0.1237 | likely_benign | 0.161 | benign | -0.607 | Destabilizing | 0.513 | D | 0.458 | neutral | N | 0.497445461 | None | None | N |
| D/H | 0.2295 | likely_benign | 0.313 | benign | -0.441 | Destabilizing | 0.986 | D | 0.529 | neutral | N | 0.521495756 | None | None | N |
| D/I | 0.2676 | likely_benign | 0.3711 | ambiguous | 0.337 | Stabilizing | 0.99 | D | 0.687 | prob.neutral | None | None | None | None | N |
| D/K | 0.3117 | likely_benign | 0.3993 | ambiguous | -0.054 | Destabilizing | 0.874 | D | 0.447 | neutral | None | None | None | None | N |
| D/L | 0.274 | likely_benign | 0.3583 | ambiguous | 0.337 | Stabilizing | 0.98 | D | 0.604 | neutral | None | None | None | None | N |
| D/M | 0.4574 | ambiguous | 0.5653 | pathogenic | 0.668 | Stabilizing | 0.998 | D | 0.687 | prob.neutral | None | None | None | None | N |
| D/N | 0.0839 | likely_benign | 0.1063 | benign | -0.358 | Destabilizing | 0.785 | D | 0.479 | neutral | N | 0.471797655 | None | None | N |
| D/P | 0.7355 | likely_pathogenic | 0.811 | pathogenic | 0.136 | Stabilizing | 0.66 | D | 0.475 | neutral | None | None | None | None | N |
| D/Q | 0.2564 | likely_benign | 0.311 | benign | -0.272 | Destabilizing | 0.901 | D | 0.443 | neutral | None | None | None | None | N |
| D/R | 0.3389 | likely_benign | 0.441 | ambiguous | 0.058 | Stabilizing | 0.98 | D | 0.617 | neutral | None | None | None | None | N |
| D/S | 0.0859 | likely_benign | 0.1205 | benign | -0.508 | Destabilizing | 0.049 | N | 0.293 | neutral | None | None | None | None | N |
| D/T | 0.1572 | likely_benign | 0.2139 | benign | -0.3 | Destabilizing | 0.462 | N | 0.467 | neutral | None | None | None | None | N |
| D/V | 0.1655 | likely_benign | 0.2245 | benign | 0.136 | Stabilizing | 0.865 | D | 0.603 | neutral | N | 0.471933728 | None | None | N |
| D/W | 0.8219 | likely_pathogenic | 0.8854 | pathogenic | -0.148 | Destabilizing | 0.999 | D | 0.747 | deleterious | None | None | None | None | N |
| D/Y | 0.2177 | likely_benign | 0.2937 | benign | -0.036 | Destabilizing | 0.998 | D | 0.691 | prob.neutral | N | 0.510625402 | 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.