Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21358 | 64297;64298;64299 | chr2:178587139;178587138;178587137 | chr2:179451866;179451865;179451864 |
| N2AB | 19717 | 59374;59375;59376 | chr2:178587139;178587138;178587137 | chr2:179451866;179451865;179451864 |
| N2A | 18790 | 56593;56594;56595 | chr2:178587139;178587138;178587137 | chr2:179451866;179451865;179451864 |
| N2B | 12293 | 37102;37103;37104 | chr2:178587139;178587138;178587137 | chr2:179451866;179451865;179451864 |
| Novex-1 | 12418 | 37477;37478;37479 | chr2:178587139;178587138;178587137 | chr2:179451866;179451865;179451864 |
| Novex-2 | 12485 | 37678;37679;37680 | chr2:178587139;178587138;178587137 | chr2:179451866;179451865;179451864 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/M | rs371725212  |
-0.419 | 0.808 | N | 0.647 | 0.097 | None | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.11E-05 | 0 |
| V/M | rs371725212 |
-0.419 | 0.808 | N | 0.647 | 0.097 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| V/M | rs371725212 |
-0.419 | 0.808 | N | 0.647 | 0.097 | None | gnomAD-4.0.0 | 2.17963E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.56946E-05 | 0 | 3.83245E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3252 | likely_benign | 0.2871 | benign | -1.872 | Destabilizing | 0.332 | N | 0.547 | neutral | N | 0.512168905 | None | None | N |
| V/C | 0.6419 | likely_pathogenic | 0.6393 | pathogenic | -1.184 | Destabilizing | 0.992 | D | 0.678 | prob.neutral | None | None | None | None | N |
| V/D | 0.837 | likely_pathogenic | 0.7857 | pathogenic | -2.39 | Highly Destabilizing | 0.972 | D | 0.796 | deleterious | None | None | None | None | N |
| V/E | 0.6376 | likely_pathogenic | 0.5891 | pathogenic | -2.165 | Highly Destabilizing | 0.963 | D | 0.644 | neutral | N | 0.476470893 | None | None | N |
| V/F | 0.1748 | likely_benign | 0.1762 | benign | -1.129 | Destabilizing | 0.444 | N | 0.653 | prob.neutral | None | None | None | None | N |
| V/G | 0.4952 | ambiguous | 0.4265 | ambiguous | -2.383 | Highly Destabilizing | 0.895 | D | 0.703 | prob.delet. | N | 0.476977872 | None | None | N |
| V/H | 0.6932 | likely_pathogenic | 0.6809 | pathogenic | -1.984 | Destabilizing | 0.848 | D | 0.788 | deleterious | None | None | None | None | N |
| V/I | 0.0743 | likely_benign | 0.0761 | benign | -0.447 | Destabilizing | 0.005 | N | 0.182 | neutral | None | None | None | None | N |
| V/K | 0.6628 | likely_pathogenic | 0.6095 | pathogenic | -1.628 | Destabilizing | 0.919 | D | 0.637 | neutral | None | None | None | None | N |
| V/L | 0.1857 | likely_benign | 0.17 | benign | -0.447 | Destabilizing | 0.079 | N | 0.453 | neutral | N | 0.467241905 | None | None | N |
| V/M | 0.1677 | likely_benign | 0.1716 | benign | -0.361 | Destabilizing | 0.808 | D | 0.647 | neutral | N | 0.505571007 | None | None | N |
| V/N | 0.6451 | likely_pathogenic | 0.5933 | pathogenic | -1.984 | Destabilizing | 0.972 | D | 0.807 | deleterious | None | None | None | None | N |
| V/P | 0.9469 | likely_pathogenic | 0.9196 | pathogenic | -0.896 | Destabilizing | 0.972 | D | 0.737 | deleterious | None | None | None | None | N |
| V/Q | 0.521 | ambiguous | 0.4892 | ambiguous | -1.827 | Destabilizing | 0.972 | D | 0.747 | deleterious | None | None | None | None | N |
| V/R | 0.5812 | likely_pathogenic | 0.5117 | ambiguous | -1.457 | Destabilizing | 0.919 | D | 0.809 | deleterious | None | None | None | None | N |
| V/S | 0.443 | ambiguous | 0.3869 | ambiguous | -2.566 | Highly Destabilizing | 0.919 | D | 0.66 | prob.neutral | None | None | None | None | N |
| V/T | 0.3009 | likely_benign | 0.2762 | benign | -2.195 | Highly Destabilizing | 0.615 | D | 0.603 | neutral | None | None | None | None | N |
| V/W | 0.8238 | likely_pathogenic | 0.8351 | pathogenic | -1.608 | Destabilizing | 0.977 | D | 0.803 | deleterious | None | None | None | None | N |
| V/Y | 0.5459 | ambiguous | 0.5529 | ambiguous | -1.181 | Destabilizing | 0.009 | N | 0.335 | 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.