Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25087 | 75484;75485;75486 | chr2:178570873;178570872;178570871 | chr2:179435600;179435599;179435598 |
| N2AB | 23446 | 70561;70562;70563 | chr2:178570873;178570872;178570871 | chr2:179435600;179435599;179435598 |
| N2A | 22519 | 67780;67781;67782 | chr2:178570873;178570872;178570871 | chr2:179435600;179435599;179435598 |
| N2B | 16022 | 48289;48290;48291 | chr2:178570873;178570872;178570871 | chr2:179435600;179435599;179435598 |
| Novex-1 | 16147 | 48664;48665;48666 | chr2:178570873;178570872;178570871 | chr2:179435600;179435599;179435598 |
| Novex-2 | 16214 | 48865;48866;48867 | chr2:178570873;178570872;178570871 | chr2:179435600;179435599;179435598 |
| 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 | rs759110420  |
-0.291 | 0.999 | D | 0.819 | 0.436 | 0.400899426204 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| A/P | rs759110420 |
-0.291 | 0.999 | D | 0.819 | 0.436 | 0.400899426204 | gnomAD-4.0.0 | 6.84306E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65689E-05 |
| A/T | rs759110420 |
-0.405 | 0.992 | N | 0.769 | 0.348 | None | gnomAD-2.1.1 | 5.72E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.14E-05 | None | 0 | None | 0 | 1.17349E-04 | 0 |
| A/T | rs759110420 |
-0.405 | 0.992 | N | 0.769 | 0.348 | None | gnomAD-3.1.2 | 8.55E-05 | None | None | None | None | I | None | 4.83E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47063E-04 | 0 | 0 |
| A/T | rs759110420 |
-0.405 | 0.992 | N | 0.769 | 0.348 | None | gnomAD-4.0.0 | 5.95011E-05 | None | None | None | None | I | None | 4.00705E-05 | 1.66733E-05 | None | 0 | 4.46209E-05 | None | 0 | 1.64528E-04 | 7.37519E-05 | 2.19592E-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 | 0.6542 | likely_pathogenic | 0.6633 | pathogenic | -0.757 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | I |
| A/D | 0.8761 | likely_pathogenic | 0.886 | pathogenic | -0.434 | Destabilizing | 0.998 | D | 0.851 | deleterious | None | None | None | None | I |
| A/E | 0.8238 | likely_pathogenic | 0.8308 | pathogenic | -0.596 | Destabilizing | 0.994 | D | 0.806 | deleterious | N | 0.488890382 | None | None | I |
| A/F | 0.6182 | likely_pathogenic | 0.6197 | pathogenic | -0.907 | Destabilizing | 0.991 | D | 0.867 | deleterious | None | None | None | None | I |
| A/G | 0.3256 | likely_benign | 0.3365 | benign | -0.213 | Destabilizing | 0.979 | D | 0.665 | neutral | N | 0.499993198 | None | None | I |
| A/H | 0.8769 | likely_pathogenic | 0.8773 | pathogenic | -0.205 | Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | I |
| A/I | 0.4675 | ambiguous | 0.4493 | ambiguous | -0.367 | Destabilizing | 0.938 | D | 0.741 | deleterious | None | None | None | None | I |
| A/K | 0.9252 | likely_pathogenic | 0.9227 | pathogenic | -0.432 | Destabilizing | 0.995 | D | 0.805 | deleterious | None | None | None | None | I |
| A/L | 0.3821 | ambiguous | 0.3758 | ambiguous | -0.367 | Destabilizing | 0.938 | D | 0.603 | neutral | None | None | None | None | I |
| A/M | 0.4661 | ambiguous | 0.4658 | ambiguous | -0.366 | Destabilizing | 0.999 | D | 0.823 | deleterious | None | None | None | None | I |
| A/N | 0.7107 | likely_pathogenic | 0.7245 | pathogenic | -0.17 | Destabilizing | 0.998 | D | 0.867 | deleterious | None | None | None | None | I |
| A/P | 0.9379 | likely_pathogenic | 0.9305 | pathogenic | -0.283 | Destabilizing | 0.999 | D | 0.819 | deleterious | D | 0.532660217 | None | None | I |
| A/Q | 0.7838 | likely_pathogenic | 0.7843 | pathogenic | -0.471 | Destabilizing | 0.998 | D | 0.832 | deleterious | None | None | None | None | I |
| A/R | 0.838 | likely_pathogenic | 0.8314 | pathogenic | 0.033 | Stabilizing | 0.995 | D | 0.835 | deleterious | None | None | None | None | I |
| A/S | 0.158 | likely_benign | 0.1739 | benign | -0.359 | Destabilizing | 0.992 | D | 0.658 | neutral | N | 0.481448097 | None | None | I |
| A/T | 0.2499 | likely_benign | 0.257 | benign | -0.446 | Destabilizing | 0.992 | D | 0.769 | deleterious | N | 0.486056453 | None | None | I |
| A/V | 0.2138 | likely_benign | 0.2087 | benign | -0.283 | Destabilizing | 0.142 | N | 0.456 | neutral | N | 0.470842357 | None | None | I |
| A/W | 0.9461 | likely_pathogenic | 0.9459 | pathogenic | -1.006 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | I |
| A/Y | 0.8509 | likely_pathogenic | 0.8516 | pathogenic | -0.663 | Destabilizing | 0.995 | D | 0.873 | deleterious | 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.