Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15166 | 45721;45722;45723 | chr2:178621222;178621221;178621220 | chr2:179485949;179485948;179485947 |
| N2AB | 13525 | 40798;40799;40800 | chr2:178621222;178621221;178621220 | chr2:179485949;179485948;179485947 |
| N2A | 12598 | 38017;38018;38019 | chr2:178621222;178621221;178621220 | chr2:179485949;179485948;179485947 |
| N2B | 6101 | 18526;18527;18528 | chr2:178621222;178621221;178621220 | chr2:179485949;179485948;179485947 |
| Novex-1 | 6226 | 18901;18902;18903 | chr2:178621222;178621221;178621220 | chr2:179485949;179485948;179485947 |
| Novex-2 | 6293 | 19102;19103;19104 | chr2:178621222;178621221;178621220 | chr2:179485949;179485948;179485947 |
| 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/N | None | None | 0.98 | N | 0.429 | 0.252 | 0.412587454835 | gnomAD-4.0.0 | 1.59415E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86254E-06 | 0 | 0 |
| D/V | rs2154211726  |
None | 0.994 | N | 0.536 | 0.448 | 0.552698843619 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/V | rs2154211726 |
None | 0.994 | N | 0.536 | 0.448 | 0.552698843619 | gnomAD-4.0.0 | 6.58111E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47314E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2117 | likely_benign | 0.1776 | benign | -0.819 | Destabilizing | 0.961 | D | 0.489 | neutral | N | 0.488826372 | None | None | N |
| D/C | 0.7869 | likely_pathogenic | 0.6881 | pathogenic | -0.288 | Destabilizing | 1.0 | D | 0.66 | neutral | None | None | None | None | N |
| D/E | 0.1499 | likely_benign | 0.1353 | benign | -0.655 | Destabilizing | 0.26 | N | 0.099 | neutral | N | 0.382756714 | None | None | N |
| D/F | 0.7655 | likely_pathogenic | 0.6953 | pathogenic | -0.582 | Destabilizing | 0.999 | D | 0.627 | neutral | None | None | None | None | N |
| D/G | 0.3434 | ambiguous | 0.3029 | benign | -1.147 | Destabilizing | 0.98 | D | 0.393 | neutral | N | 0.50518827 | None | None | N |
| D/H | 0.3385 | likely_benign | 0.2761 | benign | -0.853 | Destabilizing | 0.994 | D | 0.511 | neutral | N | 0.478014331 | None | None | N |
| D/I | 0.431 | ambiguous | 0.3604 | ambiguous | 0.05 | Stabilizing | 0.999 | D | 0.619 | neutral | None | None | None | None | N |
| D/K | 0.4495 | ambiguous | 0.4001 | ambiguous | -0.264 | Destabilizing | 0.942 | D | 0.428 | neutral | None | None | None | None | N |
| D/L | 0.4897 | ambiguous | 0.4258 | ambiguous | 0.05 | Stabilizing | 0.991 | D | 0.531 | neutral | None | None | None | None | N |
| D/M | 0.6833 | likely_pathogenic | 0.5989 | pathogenic | 0.556 | Stabilizing | 1.0 | D | 0.612 | neutral | None | None | None | None | N |
| D/N | 0.1184 | likely_benign | 0.1051 | benign | -0.691 | Destabilizing | 0.98 | D | 0.429 | neutral | N | 0.477604497 | None | None | N |
| D/P | 0.9803 | likely_pathogenic | 0.9758 | pathogenic | -0.217 | Destabilizing | 0.999 | D | 0.433 | neutral | None | None | None | None | N |
| D/Q | 0.3527 | ambiguous | 0.2998 | benign | -0.593 | Destabilizing | 0.559 | D | 0.157 | neutral | None | None | None | None | N |
| D/R | 0.5045 | ambiguous | 0.4329 | ambiguous | -0.207 | Destabilizing | 0.991 | D | 0.483 | neutral | None | None | None | None | N |
| D/S | 0.1434 | likely_benign | 0.1173 | benign | -0.986 | Destabilizing | 0.97 | D | 0.405 | neutral | None | None | None | None | N |
| D/T | 0.2311 | likely_benign | 0.1886 | benign | -0.701 | Destabilizing | 0.985 | D | 0.415 | neutral | None | None | None | None | N |
| D/V | 0.2498 | likely_benign | 0.2117 | benign | -0.217 | Destabilizing | 0.994 | D | 0.536 | neutral | N | 0.452361111 | None | None | N |
| D/W | 0.9542 | likely_pathogenic | 0.9302 | pathogenic | -0.378 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| D/Y | 0.4008 | ambiguous | 0.3497 | ambiguous | -0.311 | Destabilizing | 0.998 | D | 0.628 | neutral | N | 0.512474571 | 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.