Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30833 | 92722;92723;92724 | chr2:178549129;178549128;178549127 | chr2:179413856;179413855;179413854 |
| N2AB | 29192 | 87799;87800;87801 | chr2:178549129;178549128;178549127 | chr2:179413856;179413855;179413854 |
| N2A | 28265 | 85018;85019;85020 | chr2:178549129;178549128;178549127 | chr2:179413856;179413855;179413854 |
| N2B | 21768 | 65527;65528;65529 | chr2:178549129;178549128;178549127 | chr2:179413856;179413855;179413854 |
| Novex-1 | 21893 | 65902;65903;65904 | chr2:178549129;178549128;178549127 | chr2:179413856;179413855;179413854 |
| Novex-2 | 21960 | 66103;66104;66105 | chr2:178549129;178549128;178549127 | chr2:179413856;179413855;179413854 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs727505334  |
0.033 | 0.994 | N | 0.511 | 0.37 | 0.328222422547 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs727505334 |
0.033 | 0.994 | N | 0.511 | 0.37 | 0.328222422547 | gnomAD-4.0.0 | 1.59115E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77346E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1564 | likely_benign | 0.1535 | benign | -0.774 | Destabilizing | 0.835 | D | 0.346 | neutral | N | 0.504434856 | None | None | N |
| T/C | 0.4665 | ambiguous | 0.4525 | ambiguous | -0.692 | Destabilizing | 1.0 | D | 0.528 | neutral | None | None | None | None | N |
| T/D | 0.8257 | likely_pathogenic | 0.8203 | pathogenic | -0.929 | Destabilizing | 0.97 | D | 0.481 | neutral | None | None | None | None | N |
| T/E | 0.7564 | likely_pathogenic | 0.7437 | pathogenic | -0.953 | Destabilizing | 0.97 | D | 0.477 | neutral | None | None | None | None | N |
| T/F | 0.3965 | ambiguous | 0.349 | ambiguous | -1.357 | Destabilizing | 0.999 | D | 0.656 | neutral | None | None | None | None | N |
| T/G | 0.5095 | ambiguous | 0.4977 | ambiguous | -0.933 | Destabilizing | 0.97 | D | 0.53 | neutral | None | None | None | None | N |
| T/H | 0.4545 | ambiguous | 0.4188 | ambiguous | -1.472 | Destabilizing | 1.0 | D | 0.635 | neutral | None | None | None | None | N |
| T/I | 0.2907 | likely_benign | 0.27 | benign | -0.448 | Destabilizing | 0.994 | D | 0.511 | neutral | N | 0.426587361 | None | None | N |
| T/K | 0.5848 | likely_pathogenic | 0.5566 | ambiguous | -0.549 | Destabilizing | 0.961 | D | 0.479 | neutral | N | 0.516633362 | None | None | N |
| T/L | 0.2414 | likely_benign | 0.2203 | benign | -0.448 | Destabilizing | 0.985 | D | 0.465 | neutral | None | None | None | None | N |
| T/M | 0.1456 | likely_benign | 0.1325 | benign | 0.031 | Stabilizing | 1.0 | D | 0.528 | neutral | None | None | None | None | N |
| T/N | 0.3407 | ambiguous | 0.3211 | benign | -0.609 | Destabilizing | 0.97 | D | 0.432 | neutral | None | None | None | None | N |
| T/P | 0.696 | likely_pathogenic | 0.6857 | pathogenic | -0.53 | Destabilizing | 0.994 | D | 0.517 | neutral | N | 0.474179942 | None | None | N |
| T/Q | 0.5414 | ambiguous | 0.5177 | ambiguous | -0.959 | Destabilizing | 0.996 | D | 0.537 | neutral | None | None | None | None | N |
| T/R | 0.4945 | ambiguous | 0.4754 | ambiguous | -0.296 | Destabilizing | 0.994 | D | 0.531 | neutral | N | 0.471684726 | None | None | N |
| T/S | 0.1417 | likely_benign | 0.1395 | benign | -0.744 | Destabilizing | 0.287 | N | 0.173 | neutral | N | 0.471381075 | None | None | N |
| T/V | 0.2186 | likely_benign | 0.2076 | benign | -0.53 | Destabilizing | 0.985 | D | 0.423 | neutral | None | None | None | None | N |
| T/W | 0.7803 | likely_pathogenic | 0.7531 | pathogenic | -1.319 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | N |
| T/Y | 0.4286 | ambiguous | 0.3826 | ambiguous | -0.987 | Destabilizing | 0.999 | D | 0.656 | 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.