Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30069 | 90430;90431;90432 | chr2:178552695;178552694;178552693 | chr2:179417422;179417421;179417420 |
| N2AB | 28428 | 85507;85508;85509 | chr2:178552695;178552694;178552693 | chr2:179417422;179417421;179417420 |
| N2A | 27501 | 82726;82727;82728 | chr2:178552695;178552694;178552693 | chr2:179417422;179417421;179417420 |
| N2B | 21004 | 63235;63236;63237 | chr2:178552695;178552694;178552693 | chr2:179417422;179417421;179417420 |
| Novex-1 | 21129 | 63610;63611;63612 | chr2:178552695;178552694;178552693 | chr2:179417422;179417421;179417420 |
| Novex-2 | 21196 | 63811;63812;63813 | chr2:178552695;178552694;178552693 | chr2:179417422;179417421;179417420 |
| 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/S | rs207462678  |
-2.478 | 0.01 | N | 0.311 | 0.168 | 0.173771789658 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 1.14758E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/S | rs207462678 |
-2.478 | 0.01 | N | 0.311 | 0.168 | 0.173771789658 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | rs207462678 |
-2.478 | 0.01 | N | 0.311 | 0.168 | 0.173771789658 | gnomAD-4.0.0 | 3.09824E-06 | None | None | None | None | N | None | 5.33746E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47564E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6379 | likely_pathogenic | 0.5347 | ambiguous | -1.932 | Destabilizing | 0.176 | N | 0.384 | neutral | None | None | None | None | N |
| R/C | 0.2056 | likely_benign | 0.1681 | benign | -1.913 | Destabilizing | 0.995 | D | 0.677 | prob.neutral | None | None | None | None | N |
| R/D | 0.9369 | likely_pathogenic | 0.8896 | pathogenic | -0.563 | Destabilizing | 0.704 | D | 0.618 | neutral | None | None | None | None | N |
| R/E | 0.5788 | likely_pathogenic | 0.4699 | ambiguous | -0.349 | Destabilizing | 0.329 | N | 0.378 | neutral | None | None | None | None | N |
| R/F | 0.6942 | likely_pathogenic | 0.5999 | pathogenic | -1.388 | Destabilizing | 0.981 | D | 0.691 | prob.neutral | None | None | None | None | N |
| R/G | 0.5201 | ambiguous | 0.3977 | ambiguous | -2.291 | Highly Destabilizing | 0.27 | N | 0.539 | neutral | N | 0.50074119 | None | None | N |
| R/H | 0.188 | likely_benign | 0.1502 | benign | -2.076 | Highly Destabilizing | 0.981 | D | 0.614 | neutral | None | None | None | None | N |
| R/I | 0.3556 | ambiguous | 0.2839 | benign | -0.901 | Destabilizing | 0.944 | D | 0.713 | prob.delet. | None | None | None | None | N |
| R/K | 0.1074 | likely_benign | 0.0888 | benign | -1.225 | Destabilizing | 0.001 | N | 0.16 | neutral | N | 0.384858169 | None | None | N |
| R/L | 0.401 | ambiguous | 0.3205 | benign | -0.901 | Destabilizing | 0.495 | N | 0.557 | neutral | None | None | None | None | N |
| R/M | 0.2935 | likely_benign | 0.2373 | benign | -1.312 | Destabilizing | 0.975 | D | 0.659 | neutral | N | 0.455854262 | None | None | N |
| R/N | 0.8206 | likely_pathogenic | 0.7325 | pathogenic | -1.209 | Destabilizing | 0.495 | N | 0.434 | neutral | None | None | None | None | N |
| R/P | 0.9789 | likely_pathogenic | 0.9638 | pathogenic | -1.231 | Destabilizing | 0.828 | D | 0.671 | neutral | None | None | None | None | N |
| R/Q | 0.1135 | likely_benign | 0.0948 | benign | -1.199 | Destabilizing | 0.704 | D | 0.496 | neutral | None | None | None | None | N |
| R/S | 0.7044 | likely_pathogenic | 0.6045 | pathogenic | -2.283 | Highly Destabilizing | 0.01 | N | 0.311 | neutral | N | 0.448408215 | None | None | N |
| R/T | 0.3782 | ambiguous | 0.3161 | benign | -1.834 | Destabilizing | 0.27 | N | 0.464 | neutral | N | 0.493313785 | None | None | N |
| R/V | 0.4462 | ambiguous | 0.374 | ambiguous | -1.231 | Destabilizing | 0.704 | D | 0.641 | neutral | None | None | None | None | N |
| R/W | 0.2684 | likely_benign | 0.2111 | benign | -0.81 | Destabilizing | 0.993 | D | 0.685 | prob.neutral | N | 0.486886458 | None | None | N |
| R/Y | 0.4912 | ambiguous | 0.4106 | ambiguous | -0.677 | Destabilizing | 0.981 | D | 0.706 | prob.neutral | None | None | 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.