Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5386 | 16381;16382;16383 | chr2:178733020;178733019;178733018 | chr2:179597747;179597746;179597745 |
| N2AB | 5069 | 15430;15431;15432 | chr2:178733020;178733019;178733018 | chr2:179597747;179597746;179597745 |
| N2A | 4142 | 12649;12650;12651 | chr2:178733020;178733019;178733018 | chr2:179597747;179597746;179597745 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 | 0.005 | N | 0.137 | 0.306 | 0.295623431141 | gnomAD-4.0.0 | 1.44039E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.44375E-05 | 0 | 3.66327E-05 |
| M/L | None | None | 0.136 | N | 0.317 | 0.297 | 0.419461527279 | gnomAD-4.0.0 | 1.36867E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79906E-06 | 0 | 0 |
| M/T | rs375417155  |
-1.75 | 0.801 | N | 0.589 | 0.426 | None | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 4.45E-05 | 0 |
| M/T | rs375417155 |
-1.75 | 0.801 | N | 0.589 | 0.426 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 4.78469E-04 |
| M/T | rs375417155 |
-1.75 | 0.801 | N | 0.589 | 0.426 | None | gnomAD-4.0.0 | 2.16929E-05 | None | None | None | None | I | None | 1.33494E-05 | 0 | None | 0 | 0 | None | 0 | 1.64528E-04 | 2.62775E-05 | 1.09801E-05 | 1.60159E-05 |
| M/V | rs567457007 |
-1.59 | 0.267 | N | 0.361 | 0.329 | None | gnomAD-2.1.1 | 2.86E-05 | None | None | None | None | I | None | 3.30989E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/V | rs567457007 |
-1.59 | 0.267 | N | 0.361 | 0.329 | None | gnomAD-3.1.2 | 6.58E-05 | None | None | None | None | I | None | 2.41383E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/V | rs567457007 |
-1.59 | 0.267 | N | 0.361 | 0.329 | None | gnomAD-4.0.0 | 2.10724E-05 | None | None | None | None | I | None | 3.73264E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 9.60615E-05 |
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 | 0.7582 | likely_pathogenic | 0.7678 | pathogenic | -2.174 | Highly Destabilizing | 0.688 | D | 0.529 | neutral | None | None | None | None | I |
| M/C | 0.9113 | likely_pathogenic | 0.9127 | pathogenic | -1.553 | Destabilizing | 0.998 | D | 0.621 | neutral | None | None | None | None | I |
| M/D | 0.9923 | likely_pathogenic | 0.9927 | pathogenic | -0.741 | Destabilizing | 0.991 | D | 0.693 | prob.neutral | None | None | None | None | I |
| M/E | 0.9425 | likely_pathogenic | 0.9372 | pathogenic | -0.621 | Destabilizing | 0.991 | D | 0.676 | prob.neutral | None | None | None | None | I |
| M/F | 0.5561 | ambiguous | 0.581 | pathogenic | -0.841 | Destabilizing | 0.842 | D | 0.587 | neutral | None | None | None | None | I |
| M/G | 0.9219 | likely_pathogenic | 0.9275 | pathogenic | -2.587 | Highly Destabilizing | 0.971 | D | 0.691 | prob.neutral | None | None | None | None | I |
| M/H | 0.9562 | likely_pathogenic | 0.9576 | pathogenic | -1.73 | Destabilizing | 0.998 | D | 0.597 | neutral | None | None | None | None | I |
| M/I | 0.4854 | ambiguous | 0.4222 | ambiguous | -1.043 | Destabilizing | 0.005 | N | 0.137 | neutral | N | 0.366323628 | None | None | I |
| M/K | 0.8482 | likely_pathogenic | 0.8316 | pathogenic | -0.851 | Destabilizing | 0.891 | D | 0.639 | neutral | N | 0.511316048 | None | None | I |
| M/L | 0.1422 | likely_benign | 0.1398 | benign | -1.043 | Destabilizing | 0.136 | N | 0.317 | neutral | N | 0.449630084 | None | None | I |
| M/N | 0.9513 | likely_pathogenic | 0.9532 | pathogenic | -0.843 | Destabilizing | 0.991 | D | 0.669 | neutral | None | None | None | None | I |
| M/P | 0.8923 | likely_pathogenic | 0.8958 | pathogenic | -1.396 | Destabilizing | 0.991 | D | 0.66 | neutral | None | None | None | None | I |
| M/Q | 0.7683 | likely_pathogenic | 0.7623 | pathogenic | -0.75 | Destabilizing | 0.991 | D | 0.621 | neutral | None | None | None | None | I |
| M/R | 0.8377 | likely_pathogenic | 0.8239 | pathogenic | -0.616 | Destabilizing | 0.989 | D | 0.68 | prob.neutral | N | 0.512009481 | None | None | I |
| M/S | 0.8549 | likely_pathogenic | 0.8667 | pathogenic | -1.559 | Destabilizing | 0.915 | D | 0.601 | neutral | None | None | None | None | I |
| M/T | 0.7155 | likely_pathogenic | 0.7165 | pathogenic | -1.308 | Destabilizing | 0.801 | D | 0.589 | neutral | N | 0.471258937 | None | None | I |
| M/V | 0.1235 | likely_benign | 0.1145 | benign | -1.396 | Destabilizing | 0.267 | N | 0.361 | neutral | N | 0.425582575 | None | None | I |
| M/W | 0.9253 | likely_pathogenic | 0.9255 | pathogenic | -0.843 | Destabilizing | 0.998 | D | 0.598 | neutral | None | None | None | None | I |
| M/Y | 0.9068 | likely_pathogenic | 0.9086 | pathogenic | -0.904 | Destabilizing | 0.991 | D | 0.675 | 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.