Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7482 | 22669;22670;22671 | chr2:178722343;178722342;178722341 | chr2:179587070;179587069;179587068 |
| N2AB | 7165 | 21718;21719;21720 | chr2:178722343;178722342;178722341 | chr2:179587070;179587069;179587068 |
| N2A | 6238 | 18937;18938;18939 | chr2:178722343;178722342;178722341 | chr2:179587070;179587069;179587068 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/H | None | None | 0.969 | D | 0.407 | 0.328 | 0.339074221408 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/V | rs558855070  |
0.202 | 0.67 | N | 0.501 | 0.304 | 0.610711448424 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 6.49E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/V | rs558855070 |
0.202 | 0.67 | N | 0.501 | 0.304 | 0.610711448424 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/V | rs558855070 |
0.202 | 0.67 | N | 0.501 | 0.304 | 0.610711448424 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| D/V | rs558855070 |
0.202 | 0.67 | N | 0.501 | 0.304 | 0.610711448424 | gnomAD-4.0.0 | 2.56379E-06 | None | None | None | None | I | None | 1.68982E-05 | 0 | None | 0 | 0 | None | 0 | 2.25632E-04 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1489 | likely_benign | 0.1616 | benign | -0.471 | Destabilizing | 0.018 | N | 0.169 | neutral | N | 0.514356353 | None | None | I |
| D/C | 0.6568 | likely_pathogenic | 0.6484 | pathogenic | -0.016 | Destabilizing | 0.99 | D | 0.473 | neutral | None | None | None | None | I |
| D/E | 0.1503 | likely_benign | 0.1565 | benign | -0.408 | Destabilizing | None | N | 0.111 | neutral | N | 0.44232011 | None | None | I |
| D/F | 0.5549 | ambiguous | 0.5664 | pathogenic | -0.369 | Destabilizing | 0.997 | D | 0.507 | neutral | None | None | None | None | I |
| D/G | 0.1678 | likely_benign | 0.1706 | benign | -0.707 | Destabilizing | 0.491 | N | 0.396 | neutral | N | 0.501216485 | None | None | I |
| D/H | 0.2075 | likely_benign | 0.2203 | benign | -0.403 | Destabilizing | 0.969 | D | 0.407 | neutral | D | 0.535771775 | None | None | I |
| D/I | 0.3433 | ambiguous | 0.3712 | ambiguous | 0.117 | Stabilizing | 0.991 | D | 0.508 | neutral | None | None | None | None | I |
| D/K | 0.282 | likely_benign | 0.2777 | benign | 0.013 | Stabilizing | 0.08 | N | 0.137 | neutral | None | None | None | None | I |
| D/L | 0.3467 | ambiguous | 0.367 | ambiguous | 0.117 | Stabilizing | 0.939 | D | 0.493 | neutral | None | None | None | None | I |
| D/M | 0.5451 | ambiguous | 0.5745 | pathogenic | 0.419 | Stabilizing | 0.992 | D | 0.474 | neutral | None | None | None | None | I |
| D/N | 0.0824 | likely_benign | 0.0848 | benign | -0.256 | Destabilizing | 0.591 | D | 0.332 | neutral | N | 0.480147779 | None | None | I |
| D/P | 0.8265 | likely_pathogenic | 0.81 | pathogenic | -0.056 | Destabilizing | 0.381 | N | 0.445 | neutral | None | None | None | None | I |
| D/Q | 0.2464 | likely_benign | 0.2498 | benign | -0.203 | Destabilizing | 0.742 | D | 0.305 | neutral | None | None | None | None | I |
| D/R | 0.2863 | likely_benign | 0.2941 | benign | 0.175 | Stabilizing | 0.885 | D | 0.463 | neutral | None | None | None | None | I |
| D/S | 0.0953 | likely_benign | 0.1034 | benign | -0.406 | Destabilizing | 0.47 | N | 0.33 | neutral | None | None | None | None | I |
| D/T | 0.1994 | likely_benign | 0.2023 | benign | -0.224 | Destabilizing | 0.657 | D | 0.399 | neutral | None | None | None | None | I |
| D/V | 0.2083 | likely_benign | 0.2263 | benign | -0.056 | Destabilizing | 0.67 | D | 0.501 | neutral | N | 0.507219737 | None | None | I |
| D/W | 0.8696 | likely_pathogenic | 0.8726 | pathogenic | -0.222 | Destabilizing | 0.999 | D | 0.536 | neutral | None | None | None | None | I |
| D/Y | 0.2372 | likely_benign | 0.2439 | benign | -0.143 | Destabilizing | 0.996 | D | 0.505 | neutral | N | 0.518975526 | 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.