Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26168 | 78727;78728;78729 | chr2:178567630;178567629;178567628 | chr2:179432357;179432356;179432355 |
| N2AB | 24527 | 73804;73805;73806 | chr2:178567630;178567629;178567628 | chr2:179432357;179432356;179432355 |
| N2A | 23600 | 71023;71024;71025 | chr2:178567630;178567629;178567628 | chr2:179432357;179432356;179432355 |
| N2B | 17103 | 51532;51533;51534 | chr2:178567630;178567629;178567628 | chr2:179432357;179432356;179432355 |
| Novex-1 | 17228 | 51907;51908;51909 | chr2:178567630;178567629;178567628 | chr2:179432357;179432356;179432355 |
| Novex-2 | 17295 | 52108;52109;52110 | chr2:178567630;178567629;178567628 | chr2:179432357;179432356;179432355 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/P | None | None | 0.983 | N | 0.588 | 0.389 | 0.491996647052 | gnomAD-4.0.0 | 6.84955E-07 | None | None | None | None | I | None | 0 | 2.24095E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs755972936  |
-0.04 | 0.944 | N | 0.503 | 0.309 | 0.431490205687 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| A/V | rs755972936 |
-0.04 | 0.944 | N | 0.503 | 0.309 | 0.431490205687 | gnomAD-4.0.0 | 1.59538E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43559E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.8956 | likely_pathogenic | 0.8116 | pathogenic | -0.63 | Destabilizing | 0.999 | D | 0.531 | neutral | None | None | None | None | I |
| A/D | 0.9786 | likely_pathogenic | 0.9312 | pathogenic | -0.773 | Destabilizing | 0.95 | D | 0.523 | neutral | None | None | None | None | I |
| A/E | 0.9477 | likely_pathogenic | 0.8545 | pathogenic | -0.937 | Destabilizing | 0.056 | N | 0.377 | neutral | N | 0.499759755 | None | None | I |
| A/F | 0.8671 | likely_pathogenic | 0.7595 | pathogenic | -1.142 | Destabilizing | 0.996 | D | 0.639 | neutral | None | None | None | None | I |
| A/G | 0.4846 | ambiguous | 0.3379 | benign | -0.4 | Destabilizing | 0.025 | N | 0.231 | neutral | N | 0.515166351 | None | None | I |
| A/H | 0.9519 | likely_pathogenic | 0.9003 | pathogenic | -0.466 | Destabilizing | 0.997 | D | 0.619 | neutral | None | None | None | None | I |
| A/I | 0.8002 | likely_pathogenic | 0.5952 | pathogenic | -0.428 | Destabilizing | 0.987 | D | 0.587 | neutral | None | None | None | None | I |
| A/K | 0.9669 | likely_pathogenic | 0.9123 | pathogenic | -0.506 | Destabilizing | 0.95 | D | 0.521 | neutral | None | None | None | None | I |
| A/L | 0.6425 | likely_pathogenic | 0.4933 | ambiguous | -0.428 | Destabilizing | 0.975 | D | 0.539 | neutral | None | None | None | None | I |
| A/M | 0.7144 | likely_pathogenic | 0.5088 | ambiguous | -0.184 | Destabilizing | 0.999 | D | 0.581 | neutral | None | None | None | None | I |
| A/N | 0.8867 | likely_pathogenic | 0.7514 | pathogenic | -0.201 | Destabilizing | 0.975 | D | 0.642 | neutral | None | None | None | None | I |
| A/P | 0.9799 | likely_pathogenic | 0.9555 | pathogenic | -0.371 | Destabilizing | 0.983 | D | 0.588 | neutral | N | 0.479157146 | None | None | I |
| A/Q | 0.8827 | likely_pathogenic | 0.7753 | pathogenic | -0.569 | Destabilizing | 0.95 | D | 0.583 | neutral | None | None | None | None | I |
| A/R | 0.9132 | likely_pathogenic | 0.8455 | pathogenic | -0.005 | Destabilizing | 0.975 | D | 0.588 | neutral | None | None | None | None | I |
| A/S | 0.2696 | likely_benign | 0.1716 | benign | -0.371 | Destabilizing | 0.892 | D | 0.457 | neutral | N | 0.513843773 | None | None | I |
| A/T | 0.4659 | ambiguous | 0.2393 | benign | -0.468 | Destabilizing | 0.967 | D | 0.507 | neutral | N | 0.521673823 | None | None | I |
| A/V | 0.5943 | likely_pathogenic | 0.3329 | benign | -0.371 | Destabilizing | 0.944 | D | 0.503 | neutral | N | 0.476079272 | None | None | I |
| A/W | 0.9851 | likely_pathogenic | 0.9722 | pathogenic | -1.262 | Destabilizing | 0.999 | D | 0.696 | prob.neutral | None | None | None | None | I |
| A/Y | 0.9355 | likely_pathogenic | 0.8835 | pathogenic | -0.885 | Destabilizing | 0.996 | D | 0.636 | neutral | 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.