Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17998 | 54217;54218;54219 | chr2:178605185;178605184;178605183 | chr2:179469912;179469911;179469910 |
| N2AB | 16357 | 49294;49295;49296 | chr2:178605185;178605184;178605183 | chr2:179469912;179469911;179469910 |
| N2A | 15430 | 46513;46514;46515 | chr2:178605185;178605184;178605183 | chr2:179469912;179469911;179469910 |
| N2B | 8933 | 27022;27023;27024 | chr2:178605185;178605184;178605183 | chr2:179469912;179469911;179469910 |
| Novex-1 | 9058 | 27397;27398;27399 | chr2:178605185;178605184;178605183 | chr2:179469912;179469911;179469910 |
| Novex-2 | 9125 | 27598;27599;27600 | chr2:178605185;178605184;178605183 | chr2:179469912;179469911;179469910 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | None | None | 0.998 | N | 0.683 | 0.462 | 0.55350970329 | gnomAD-4.0.0 | 1.59424E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8629E-06 | 0 | 0 |
| I/T | rs781376870  |
-2.152 | 0.989 | N | 0.762 | 0.72 | 0.791155293085 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.98E-06 | 0 |
| I/T | rs781376870 |
-2.152 | 0.989 | N | 0.762 | 0.72 | 0.791155293085 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs781376870 |
-2.152 | 0.989 | N | 0.762 | 0.72 | 0.791155293085 | gnomAD-4.0.0 | 8.06347E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.24245E-05 | None | 0 | 0 | 7.63282E-06 | 3.29649E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6865 | likely_pathogenic | 0.7515 | pathogenic | -2.019 | Highly Destabilizing | 0.992 | D | 0.703 | prob.neutral | None | None | None | None | I |
| I/C | 0.9009 | likely_pathogenic | 0.9205 | pathogenic | -1.048 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | None | I |
| I/D | 0.9916 | likely_pathogenic | 0.9937 | pathogenic | -1.705 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | I |
| I/E | 0.966 | likely_pathogenic | 0.9715 | pathogenic | -1.668 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | I |
| I/F | 0.3168 | likely_benign | 0.3938 | ambiguous | -1.394 | Destabilizing | 0.998 | D | 0.71 | prob.delet. | D | 0.533065118 | None | None | I |
| I/G | 0.9645 | likely_pathogenic | 0.9741 | pathogenic | -2.391 | Highly Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | I |
| I/H | 0.9663 | likely_pathogenic | 0.9763 | pathogenic | -1.678 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | I |
| I/K | 0.9618 | likely_pathogenic | 0.9691 | pathogenic | -1.508 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | I |
| I/L | 0.2198 | likely_benign | 0.2496 | benign | -1.034 | Destabilizing | 0.889 | D | 0.469 | neutral | N | 0.502664853 | None | None | I |
| I/M | 0.1371 | likely_benign | 0.1559 | benign | -0.686 | Destabilizing | 0.998 | D | 0.683 | prob.neutral | N | 0.517152623 | None | None | I |
| I/N | 0.9193 | likely_pathogenic | 0.9334 | pathogenic | -1.278 | Destabilizing | 0.999 | D | 0.831 | deleterious | D | 0.532636758 | None | None | I |
| I/P | 0.9703 | likely_pathogenic | 0.9778 | pathogenic | -1.334 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | I |
| I/Q | 0.9487 | likely_pathogenic | 0.9583 | pathogenic | -1.424 | Destabilizing | 1.0 | D | 0.834 | deleterious | None | None | None | None | I |
| I/R | 0.9429 | likely_pathogenic | 0.9569 | pathogenic | -0.909 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | I |
| I/S | 0.8374 | likely_pathogenic | 0.8681 | pathogenic | -1.866 | Destabilizing | 0.998 | D | 0.813 | deleterious | N | 0.517406113 | None | None | I |
| I/T | 0.4092 | ambiguous | 0.4306 | ambiguous | -1.713 | Destabilizing | 0.989 | D | 0.762 | deleterious | N | 0.507442159 | None | None | I |
| I/V | 0.1048 | likely_benign | 0.1007 | benign | -1.334 | Destabilizing | 0.333 | N | 0.175 | neutral | N | 0.471693293 | None | None | I |
| I/W | 0.9262 | likely_pathogenic | 0.9508 | pathogenic | -1.539 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | I |
| I/Y | 0.8409 | likely_pathogenic | 0.8887 | pathogenic | -1.343 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | 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.