Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3893 | 11902;11903;11904 | chr2:178741556;178741555;178741554 | chr2:179606283;179606282;179606281 |
| N2AB | 3576 | 10951;10952;10953 | chr2:178741556;178741555;178741554 | chr2:179606283;179606282;179606281 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3530 | 10813;10814;10815 | chr2:178741556;178741555;178741554 | chr2:179606283;179606282;179606281 |
| Novex-1 | 3655 | 11188;11189;11190 | chr2:178741556;178741555;178741554 | chr2:179606283;179606282;179606281 |
| Novex-2 | 3722 | 11389;11390;11391 | chr2:178741556;178741555;178741554 | chr2:179606283;179606282;179606281 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs2154318912  |
None | None | N | 0.155 | 0.1 | None | gnomAD-4.0.0 | 3.18234E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71598E-06 | 0 | 0 |
| M/T | rs1553941782 |
None | None | N | 0.244 | 0.122 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| M/T | rs1553941782 |
None | None | N | 0.244 | 0.122 | None | gnomAD-4.0.0 | 5.57719E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.62835E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.3357 | likely_benign | 0.3093 | benign | -2.472 | Highly Destabilizing | 0.002 | N | 0.315 | neutral | None | None | None | None | I |
| M/C | 0.7231 | likely_pathogenic | 0.7049 | pathogenic | -1.899 | Destabilizing | 0.245 | N | 0.532 | neutral | None | None | None | None | I |
| M/D | 0.8123 | likely_pathogenic | 0.7774 | pathogenic | -1.61 | Destabilizing | 0.018 | N | 0.559 | neutral | None | None | None | None | I |
| M/E | 0.3176 | likely_benign | 0.3097 | benign | -1.459 | Destabilizing | 0.009 | N | 0.515 | neutral | None | None | None | None | I |
| M/F | 0.3368 | likely_benign | 0.3033 | benign | -0.989 | Destabilizing | 0.009 | N | 0.517 | neutral | None | None | None | None | I |
| M/G | 0.683 | likely_pathogenic | 0.6473 | pathogenic | -2.896 | Highly Destabilizing | 0.018 | N | 0.533 | neutral | None | None | None | None | I |
| M/H | 0.5178 | ambiguous | 0.4862 | ambiguous | -2.143 | Highly Destabilizing | 0.497 | N | 0.555 | neutral | None | None | None | None | I |
| M/I | 0.1617 | likely_benign | 0.1602 | benign | -1.283 | Destabilizing | None | N | 0.155 | neutral | N | 0.388277105 | None | None | I |
| M/K | 0.1799 | likely_benign | 0.175 | benign | -1.386 | Destabilizing | None | N | 0.295 | neutral | N | 0.42740217 | None | None | I |
| M/L | 0.1367 | likely_benign | 0.1229 | benign | -1.283 | Destabilizing | None | N | 0.147 | neutral | N | 0.448404643 | None | None | I |
| M/N | 0.5278 | ambiguous | 0.4866 | ambiguous | -1.463 | Destabilizing | 0.018 | N | 0.572 | neutral | None | None | None | None | I |
| M/P | 0.9731 | likely_pathogenic | 0.967 | pathogenic | -1.659 | Destabilizing | 0.085 | N | 0.595 | neutral | None | None | None | None | I |
| M/Q | 0.2459 | likely_benign | 0.2521 | benign | -1.343 | Destabilizing | 0.044 | N | 0.565 | neutral | None | None | None | None | I |
| M/R | 0.1811 | likely_benign | 0.17 | benign | -1.132 | Destabilizing | 0.007 | N | 0.519 | neutral | N | 0.421622848 | None | None | I |
| M/S | 0.3731 | ambiguous | 0.3458 | ambiguous | -2.13 | Highly Destabilizing | 0.004 | N | 0.378 | neutral | None | None | None | None | I |
| M/T | 0.1318 | likely_benign | 0.1256 | benign | -1.866 | Destabilizing | None | N | 0.244 | neutral | N | 0.350401895 | None | None | I |
| M/V | 0.0676 | likely_benign | 0.0676 | benign | -1.659 | Destabilizing | None | N | 0.159 | neutral | N | 0.368741949 | None | None | I |
| M/W | 0.678 | likely_pathogenic | 0.6276 | pathogenic | -1.117 | Destabilizing | 0.497 | N | 0.535 | neutral | None | None | None | None | I |
| M/Y | 0.5877 | likely_pathogenic | 0.5451 | ambiguous | -1.186 | Destabilizing | 0.085 | N | 0.587 | 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.