Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8691 | 26296;26297;26298 | chr2:178715115;178715114;178715113 | chr2:179579842;179579841;179579840 |
| N2AB | 8374 | 25345;25346;25347 | chr2:178715115;178715114;178715113 | chr2:179579842;179579841;179579840 |
| N2A | 7447 | 22564;22565;22566 | chr2:178715115;178715114;178715113 | chr2:179579842;179579841;179579840 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | None | None | 0.063 | N | 0.172 | 0.263 | 0.0986583533028 | gnomAD-4.0.0 | 1.36848E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99526E-07 | 0 | 1.65651E-05 |
| I/R | rs1354912931  |
-0.761 | 0.976 | D | 0.629 | 0.686 | 0.876083083943 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| I/R | rs1354912931 |
-0.761 | 0.976 | D | 0.629 | 0.686 | 0.876083083943 | gnomAD-4.0.0 | 6.84234E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99522E-07 | 0 | 0 |
| I/T | None | None | 0.813 | N | 0.501 | 0.442 | 0.735610994172 | gnomAD-4.0.0 | 2.0527E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69856E-06 | 0 | 0 |
| I/V | None | None | 0.001 | N | 0.145 | 0.079 | 0.544303689236 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6624 | likely_pathogenic | 0.5928 | pathogenic | -1.999 | Destabilizing | 0.798 | D | 0.373 | neutral | None | None | None | None | N |
| I/C | 0.8184 | likely_pathogenic | 0.8034 | pathogenic | -1.283 | Destabilizing | 0.122 | N | 0.282 | neutral | None | None | None | None | N |
| I/D | 0.9288 | likely_pathogenic | 0.9128 | pathogenic | -1.264 | Destabilizing | 0.998 | D | 0.648 | neutral | None | None | None | None | N |
| I/E | 0.8367 | likely_pathogenic | 0.8009 | pathogenic | -1.171 | Destabilizing | 0.99 | D | 0.643 | neutral | None | None | None | None | N |
| I/F | 0.2034 | likely_benign | 0.1741 | benign | -1.261 | Destabilizing | 0.023 | N | 0.255 | neutral | None | None | None | None | N |
| I/G | 0.8685 | likely_pathogenic | 0.8348 | pathogenic | -2.428 | Highly Destabilizing | 0.975 | D | 0.601 | neutral | None | None | None | None | N |
| I/H | 0.7594 | likely_pathogenic | 0.733 | pathogenic | -1.647 | Destabilizing | 0.998 | D | 0.619 | neutral | None | None | None | None | N |
| I/K | 0.6806 | likely_pathogenic | 0.6272 | pathogenic | -1.278 | Destabilizing | 0.751 | D | 0.642 | neutral | N | 0.515868268 | None | None | N |
| I/L | 0.1513 | likely_benign | 0.1351 | benign | -0.842 | Destabilizing | 0.016 | N | 0.265 | neutral | D | 0.530653957 | None | None | N |
| I/M | 0.1114 | likely_benign | 0.1026 | benign | -0.712 | Destabilizing | 0.063 | N | 0.172 | neutral | N | 0.487822831 | None | None | N |
| I/N | 0.5603 | ambiguous | 0.5221 | ambiguous | -1.214 | Destabilizing | 0.998 | D | 0.629 | neutral | None | None | None | None | N |
| I/P | 0.9438 | likely_pathogenic | 0.9342 | pathogenic | -1.199 | Destabilizing | 0.998 | D | 0.63 | neutral | None | None | None | None | N |
| I/Q | 0.6913 | likely_pathogenic | 0.6516 | pathogenic | -1.264 | Destabilizing | 0.983 | D | 0.633 | neutral | None | None | None | None | N |
| I/R | 0.5924 | likely_pathogenic | 0.5397 | ambiguous | -0.843 | Destabilizing | 0.976 | D | 0.629 | neutral | D | 0.523857212 | None | None | N |
| I/S | 0.6345 | likely_pathogenic | 0.5807 | pathogenic | -1.983 | Destabilizing | 0.975 | D | 0.539 | neutral | None | None | None | None | N |
| I/T | 0.506 | ambiguous | 0.4398 | ambiguous | -1.755 | Destabilizing | 0.813 | D | 0.501 | neutral | N | 0.488520848 | None | None | N |
| I/V | 0.1005 | likely_benign | 0.0935 | benign | -1.199 | Destabilizing | 0.001 | N | 0.145 | neutral | N | 0.485782885 | None | None | N |
| I/W | 0.8011 | likely_pathogenic | 0.7774 | pathogenic | -1.404 | Destabilizing | 1.0 | D | 0.634 | neutral | None | None | None | None | N |
| I/Y | 0.5649 | likely_pathogenic | 0.539 | ambiguous | -1.154 | Destabilizing | 0.61 | D | 0.587 | 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.