Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15377 | 46354;46355;46356 | chr2:178620392;178620391;178620390 | chr2:179485119;179485118;179485117 |
| N2AB | 13736 | 41431;41432;41433 | chr2:178620392;178620391;178620390 | chr2:179485119;179485118;179485117 |
| N2A | 12809 | 38650;38651;38652 | chr2:178620392;178620391;178620390 | chr2:179485119;179485118;179485117 |
| N2B | 6312 | 19159;19160;19161 | chr2:178620392;178620391;178620390 | chr2:179485119;179485118;179485117 |
| Novex-1 | 6437 | 19534;19535;19536 | chr2:178620392;178620391;178620390 | chr2:179485119;179485118;179485117 |
| Novex-2 | 6504 | 19735;19736;19737 | chr2:178620392;178620391;178620390 | chr2:179485119;179485118;179485117 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/E | None | None | 0.08 | N | 0.179 | 0.147 | 0.141422826196 | gnomAD-4.0.0 | 1.36972E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.32218E-05 | 0 |
| Q/K | None | None | 0.285 | N | 0.279 | 0.188 | 0.139678290688 | gnomAD-4.0.0 | 6.84858E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00095E-07 | 0 | 0 |
| Q/R | None | None | 0.491 | N | 0.268 | 0.142 | 0.143124449307 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/A | 0.162 | likely_benign | 0.1633 | benign | -0.118 | Destabilizing | 0.345 | N | 0.302 | neutral | None | None | None | None | N |
| Q/C | 0.6939 | likely_pathogenic | 0.7048 | pathogenic | -0.206 | Destabilizing | 0.991 | D | 0.176 | neutral | None | None | None | None | N |
| Q/D | 0.2679 | likely_benign | 0.2553 | benign | -0.268 | Destabilizing | 0.001 | N | 0.161 | neutral | None | None | None | None | N |
| Q/E | 0.0903 | likely_benign | 0.093 | benign | -0.331 | Destabilizing | 0.08 | N | 0.179 | neutral | N | 0.403613148 | None | None | N |
| Q/F | 0.6923 | likely_pathogenic | 0.6876 | pathogenic | -0.576 | Destabilizing | 0.901 | D | 0.212 | neutral | None | None | None | None | N |
| Q/G | 0.2176 | likely_benign | 0.2089 | benign | -0.191 | Destabilizing | 0.345 | N | 0.265 | neutral | None | None | None | None | N |
| Q/H | 0.2408 | likely_benign | 0.2378 | benign | 0.017 | Stabilizing | 0.003 | N | 0.211 | neutral | N | 0.451168688 | None | None | N |
| Q/I | 0.3734 | ambiguous | 0.3616 | ambiguous | -0.019 | Destabilizing | 0.901 | D | 0.259 | neutral | None | None | None | None | N |
| Q/K | 0.0853 | likely_benign | 0.0804 | benign | -0.098 | Destabilizing | 0.285 | N | 0.279 | neutral | N | 0.445569302 | None | None | N |
| Q/L | 0.167 | likely_benign | 0.1684 | benign | -0.019 | Destabilizing | 0.491 | N | 0.342 | neutral | N | 0.448100728 | None | None | N |
| Q/M | 0.3119 | likely_benign | 0.3234 | benign | -0.037 | Destabilizing | 0.965 | D | 0.225 | neutral | None | None | None | None | N |
| Q/N | 0.1972 | likely_benign | 0.1743 | benign | -0.304 | Destabilizing | 0.561 | D | 0.236 | neutral | None | None | None | None | N |
| Q/P | 0.1135 | likely_benign | 0.1155 | benign | -0.031 | Destabilizing | 0.001 | N | 0.197 | neutral | N | 0.444448097 | None | None | N |
| Q/R | 0.111 | likely_benign | 0.1158 | benign | 0.111 | Stabilizing | 0.491 | N | 0.268 | neutral | N | 0.447773458 | None | None | N |
| Q/S | 0.1635 | likely_benign | 0.1541 | benign | -0.295 | Destabilizing | 0.345 | N | 0.25 | neutral | None | None | None | None | N |
| Q/T | 0.1576 | likely_benign | 0.146 | benign | -0.25 | Destabilizing | 0.722 | D | 0.299 | neutral | None | None | None | None | N |
| Q/V | 0.2508 | likely_benign | 0.2533 | benign | -0.031 | Destabilizing | 0.722 | D | 0.337 | neutral | None | None | None | None | N |
| Q/W | 0.6282 | likely_pathogenic | 0.6552 | pathogenic | -0.667 | Destabilizing | 0.991 | D | 0.221 | neutral | None | None | None | None | N |
| Q/Y | 0.5102 | ambiguous | 0.5111 | ambiguous | -0.376 | Destabilizing | 0.692 | D | 0.279 | 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.