Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28185 | 84778;84779;84780 | chr2:178561579;178561578;178561577 | chr2:179426306;179426305;179426304 |
| N2AB | 26544 | 79855;79856;79857 | chr2:178561579;178561578;178561577 | chr2:179426306;179426305;179426304 |
| N2A | 25617 | 77074;77075;77076 | chr2:178561579;178561578;178561577 | chr2:179426306;179426305;179426304 |
| N2B | 19120 | 57583;57584;57585 | chr2:178561579;178561578;178561577 | chr2:179426306;179426305;179426304 |
| Novex-1 | 19245 | 57958;57959;57960 | chr2:178561579;178561578;178561577 | chr2:179426306;179426305;179426304 |
| Novex-2 | 19312 | 58159;58160;58161 | chr2:178561579;178561578;178561577 | chr2:179426306;179426305;179426304 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs371516793  |
0.111 | None | N | 0.065 | 0.054 | 0.0666544352282 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | I | None | 0 | 5.82E-05 | None | 0 | 1.12347E-04 | None | 6.56E-05 | None | 0 | 0 | 0 |
| R/Q | rs371516793 |
0.111 | None | N | 0.065 | 0.054 | 0.0666544352282 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 3.86548E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs371516793 |
0.111 | None | N | 0.065 | 0.054 | 0.0666544352282 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/Q | rs371516793 |
0.111 | None | N | 0.065 | 0.054 | 0.0666544352282 | gnomAD-4.0.0 | 1.85965E-05 | None | None | None | None | I | None | 3.99893E-05 | 5.00434E-05 | None | 0 | 2.68204E-04 | None | 1.56338E-05 | 0 | 4.23898E-06 | 4.39522E-05 | 3.20215E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.1409 | likely_benign | 0.1443 | benign | 0.015 | Stabilizing | 0.004 | N | 0.233 | neutral | None | None | None | None | I |
| R/C | 0.1078 | likely_benign | 0.1127 | benign | -0.293 | Destabilizing | 0.497 | N | 0.465 | neutral | None | None | None | None | I |
| R/D | 0.2865 | likely_benign | 0.2888 | benign | -0.326 | Destabilizing | 0.009 | N | 0.373 | neutral | None | None | None | None | I |
| R/E | 0.1622 | likely_benign | 0.1675 | benign | -0.296 | Destabilizing | 0.004 | N | 0.167 | neutral | None | None | None | None | I |
| R/F | 0.3459 | ambiguous | 0.3665 | ambiguous | -0.335 | Destabilizing | 0.245 | N | 0.493 | neutral | None | None | None | None | I |
| R/G | 0.1218 | likely_benign | 0.1218 | benign | -0.101 | Destabilizing | 0.008 | N | 0.372 | neutral | N | 0.463049593 | None | None | I |
| R/H | 0.0766 | likely_benign | 0.0771 | benign | -0.567 | Destabilizing | 0.138 | N | 0.315 | neutral | None | None | None | None | I |
| R/I | 0.194 | likely_benign | 0.2036 | benign | 0.272 | Stabilizing | 0.022 | N | 0.537 | neutral | None | None | None | None | I |
| R/K | 0.0714 | likely_benign | 0.0725 | benign | -0.205 | Destabilizing | None | N | 0.063 | neutral | None | None | None | None | I |
| R/L | 0.1339 | likely_benign | 0.1401 | benign | 0.272 | Stabilizing | 0.018 | N | 0.385 | neutral | N | 0.478480406 | None | None | I |
| R/M | 0.1815 | likely_benign | 0.1834 | benign | -0.131 | Destabilizing | 0.245 | N | 0.394 | neutral | None | None | None | None | I |
| R/N | 0.2213 | likely_benign | 0.2273 | benign | -0.132 | Destabilizing | None | N | 0.071 | neutral | None | None | None | None | I |
| R/P | 0.1187 | likely_benign | 0.1189 | benign | 0.203 | Stabilizing | None | N | 0.102 | neutral | N | 0.306855958 | None | None | I |
| R/Q | 0.0686 | likely_benign | 0.069 | benign | -0.159 | Destabilizing | None | N | 0.065 | neutral | N | 0.458758495 | None | None | I |
| R/S | 0.1852 | likely_benign | 0.1853 | benign | -0.286 | Destabilizing | None | N | 0.087 | neutral | None | None | None | None | I |
| R/T | 0.1178 | likely_benign | 0.1194 | benign | -0.162 | Destabilizing | 0.009 | N | 0.344 | neutral | None | None | None | None | I |
| R/V | 0.1876 | likely_benign | 0.1957 | benign | 0.203 | Stabilizing | None | N | 0.138 | neutral | None | None | None | None | I |
| R/W | 0.1523 | likely_benign | 0.1559 | benign | -0.545 | Destabilizing | 0.788 | D | 0.456 | neutral | None | None | None | None | I |
| R/Y | 0.2325 | likely_benign | 0.2399 | benign | -0.148 | Destabilizing | 0.245 | N | 0.477 | neutral | None | None | 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.