Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33219 | 99880;99881;99882 | chr2:178537552;178537551;178537550 | chr2:179402279;179402278;179402277 |
| N2AB | 31578 | 94957;94958;94959 | chr2:178537552;178537551;178537550 | chr2:179402279;179402278;179402277 |
| N2A | 30651 | 92176;92177;92178 | chr2:178537552;178537551;178537550 | chr2:179402279;179402278;179402277 |
| N2B | 24154 | 72685;72686;72687 | chr2:178537552;178537551;178537550 | chr2:179402279;179402278;179402277 |
| Novex-1 | 24279 | 73060;73061;73062 | chr2:178537552;178537551;178537550 | chr2:179402279;179402278;179402277 |
| Novex-2 | 24346 | 73261;73262;73263 | chr2:178537552;178537551;178537550 | chr2:179402279;179402278;179402277 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | None | None | 0.001 | N | 0.227 | 0.18 | 0.425028116352 | gnomAD-4.0.0 | 1.36849E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79897E-06 | 0 | 0 |
| M/R | None | None | 0.099 | N | 0.445 | 0.288 | 0.535439087667 | gnomAD-4.0.0 | 6.84242E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99484E-07 | 0 | 0 |
| M/T | rs1692183695  |
None | None | N | 0.171 | 0.241 | 0.639502115021 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92604E-04 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | rs1692183695 |
None | None | N | 0.171 | 0.241 | 0.639502115021 | gnomAD-4.0.0 | 1.73516E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.01685E-04 | None | 0 | 0 | 8.4762E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.4856 | ambiguous | 0.5083 | ambiguous | -1.717 | Destabilizing | None | N | 0.176 | neutral | None | None | None | None | N |
| M/C | 0.8043 | likely_pathogenic | 0.8125 | pathogenic | -1.11 | Destabilizing | 0.723 | D | 0.408 | neutral | None | None | None | None | N |
| M/D | 0.9477 | likely_pathogenic | 0.9275 | pathogenic | -0.779 | Destabilizing | 0.044 | N | 0.485 | neutral | None | None | None | None | N |
| M/E | 0.7562 | likely_pathogenic | 0.7099 | pathogenic | -0.73 | Destabilizing | 0.018 | N | 0.425 | neutral | None | None | None | None | N |
| M/F | 0.6336 | likely_pathogenic | 0.6272 | pathogenic | -0.712 | Destabilizing | None | N | 0.189 | neutral | None | None | None | None | N |
| M/G | 0.7935 | likely_pathogenic | 0.7786 | pathogenic | -2.007 | Highly Destabilizing | 0.032 | N | 0.433 | neutral | None | None | None | None | N |
| M/H | 0.8254 | likely_pathogenic | 0.798 | pathogenic | -0.941 | Destabilizing | 0.767 | D | 0.439 | neutral | None | None | None | None | N |
| M/I | 0.4292 | ambiguous | 0.6073 | pathogenic | -0.959 | Destabilizing | 0.001 | N | 0.227 | neutral | N | 0.3866029 | None | None | N |
| M/K | 0.4664 | ambiguous | 0.4464 | ambiguous | -0.711 | Destabilizing | 0.021 | N | 0.376 | neutral | N | 0.356431921 | None | None | N |
| M/L | 0.2055 | likely_benign | 0.2527 | benign | -0.959 | Destabilizing | 0.001 | N | 0.202 | neutral | N | 0.411383914 | None | None | N |
| M/N | 0.7153 | likely_pathogenic | 0.6795 | pathogenic | -0.682 | Destabilizing | 0.099 | N | 0.503 | neutral | None | None | None | None | N |
| M/P | 0.7563 | likely_pathogenic | 0.7305 | pathogenic | -1.188 | Destabilizing | 0.183 | N | 0.487 | neutral | None | None | None | None | N |
| M/Q | 0.456 | ambiguous | 0.4023 | ambiguous | -0.747 | Destabilizing | 0.236 | N | 0.29 | neutral | None | None | None | None | N |
| M/R | 0.4831 | ambiguous | 0.4928 | ambiguous | -0.145 | Destabilizing | 0.099 | N | 0.445 | neutral | N | 0.366803631 | None | None | N |
| M/S | 0.5941 | likely_pathogenic | 0.5526 | ambiguous | -1.214 | Destabilizing | 0.032 | N | 0.328 | neutral | None | None | None | None | N |
| M/T | 0.3685 | ambiguous | 0.4359 | ambiguous | -1.065 | Destabilizing | None | N | 0.171 | neutral | N | 0.358240076 | None | None | N |
| M/V | 0.1037 | likely_benign | 0.1828 | benign | -1.188 | Destabilizing | None | N | 0.166 | neutral | N | 0.333539206 | None | None | N |
| M/W | 0.9136 | likely_pathogenic | 0.9042 | pathogenic | -0.67 | Destabilizing | 0.922 | D | 0.426 | neutral | None | None | None | None | N |
| M/Y | 0.8512 | likely_pathogenic | 0.8171 | pathogenic | -0.704 | Destabilizing | 0.04 | N | 0.41 | neutral | 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.