Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13858 | 41797;41798;41799 | chr2:178635999;178635998;178635997 | chr2:179500726;179500725;179500724 |
| N2AB | 12217 | 36874;36875;36876 | chr2:178635999;178635998;178635997 | chr2:179500726;179500725;179500724 |
| N2A | 11290 | 34093;34094;34095 | chr2:178635999;178635998;178635997 | chr2:179500726;179500725;179500724 |
| N2B | 4793 | 14602;14603;14604 | chr2:178635999;178635998;178635997 | chr2:179500726;179500725;179500724 |
| Novex-1 | 4918 | 14977;14978;14979 | chr2:178635999;178635998;178635997 | chr2:179500726;179500725;179500724 |
| Novex-2 | 4985 | 15178;15179;15180 | chr2:178635999;178635998;178635997 | chr2:179500726;179500725;179500724 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/S | rs529917511  |
-0.257 | 0.136 | N | 0.181 | 0.136 | 0.0846915920261 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| N/S | rs529917511 |
-0.257 | 0.136 | N | 0.181 | 0.136 | 0.0846915920261 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/S | rs529917511 |
-0.257 | 0.136 | N | 0.181 | 0.136 | 0.0846915920261 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| N/S | rs529917511 |
-0.257 | 0.136 | N | 0.181 | 0.136 | 0.0846915920261 | gnomAD-4.0.0 | 6.56978E-06 | None | None | None | None | N | None | 2.40558E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.2911 | likely_benign | 0.283 | benign | -0.126 | Destabilizing | 0.525 | D | 0.319 | neutral | None | None | None | None | N |
| N/C | 0.4929 | ambiguous | 0.4594 | ambiguous | -0.066 | Destabilizing | 0.998 | D | 0.412 | neutral | None | None | None | None | N |
| N/D | 0.1187 | likely_benign | 0.1408 | benign | -0.134 | Destabilizing | 0.012 | N | 0.203 | neutral | N | 0.340128396 | None | None | N |
| N/E | 0.418 | ambiguous | 0.4234 | ambiguous | -0.207 | Destabilizing | 0.525 | D | 0.24 | neutral | None | None | None | None | N |
| N/F | 0.7753 | likely_pathogenic | 0.7689 | pathogenic | -0.791 | Destabilizing | 0.991 | D | 0.483 | neutral | None | None | None | None | N |
| N/G | 0.2551 | likely_benign | 0.261 | benign | -0.169 | Destabilizing | 0.688 | D | 0.24 | neutral | None | None | None | None | N |
| N/H | 0.1822 | likely_benign | 0.1816 | benign | -0.185 | Destabilizing | 0.989 | D | 0.391 | neutral | N | 0.348615897 | None | None | N |
| N/I | 0.5513 | ambiguous | 0.498 | ambiguous | -0.105 | Destabilizing | 0.966 | D | 0.547 | neutral | N | 0.349247676 | None | None | N |
| N/K | 0.4077 | ambiguous | 0.3939 | ambiguous | -0.081 | Destabilizing | 0.022 | N | 0.093 | neutral | N | 0.300276361 | None | None | N |
| N/L | 0.4405 | ambiguous | 0.415 | ambiguous | -0.105 | Destabilizing | 0.915 | D | 0.433 | neutral | None | None | None | None | N |
| N/M | 0.6029 | likely_pathogenic | 0.5743 | pathogenic | -0.094 | Destabilizing | 0.998 | D | 0.422 | neutral | None | None | None | None | N |
| N/P | 0.6181 | likely_pathogenic | 0.5537 | ambiguous | -0.094 | Destabilizing | 0.974 | D | 0.484 | neutral | None | None | None | None | N |
| N/Q | 0.4191 | ambiguous | 0.403 | ambiguous | -0.365 | Destabilizing | 0.842 | D | 0.39 | neutral | None | None | None | None | N |
| N/R | 0.4486 | ambiguous | 0.4363 | ambiguous | None | Stabilizing | 0.728 | D | 0.27 | neutral | None | None | None | None | N |
| N/S | 0.0894 | likely_benign | 0.0866 | benign | -0.165 | Destabilizing | 0.136 | N | 0.181 | neutral | N | 0.34194266 | None | None | N |
| N/T | 0.2376 | likely_benign | 0.2123 | benign | -0.151 | Destabilizing | 0.669 | D | 0.267 | neutral | N | 0.34545694 | None | None | N |
| N/V | 0.4702 | ambiguous | 0.4232 | ambiguous | -0.094 | Destabilizing | 0.915 | D | 0.477 | neutral | None | None | None | None | N |
| N/W | 0.895 | likely_pathogenic | 0.89 | pathogenic | -0.975 | Destabilizing | 0.998 | D | 0.539 | neutral | None | None | None | None | N |
| N/Y | 0.3284 | likely_benign | 0.3305 | benign | -0.651 | Destabilizing | 0.989 | D | 0.496 | neutral | N | 0.350117194 | 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.