Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22798 | 68617;68618;68619 | chr2:178578123;178578122;178578121 | chr2:179442850;179442849;179442848 |
| N2AB | 21157 | 63694;63695;63696 | chr2:178578123;178578122;178578121 | chr2:179442850;179442849;179442848 |
| N2A | 20230 | 60913;60914;60915 | chr2:178578123;178578122;178578121 | chr2:179442850;179442849;179442848 |
| N2B | 13733 | 41422;41423;41424 | chr2:178578123;178578122;178578121 | chr2:179442850;179442849;179442848 |
| Novex-1 | 13858 | 41797;41798;41799 | chr2:178578123;178578122;178578121 | chr2:179442850;179442849;179442848 |
| Novex-2 | 13925 | 41998;41999;42000 | chr2:178578123;178578122;178578121 | chr2:179442850;179442849;179442848 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs2046857327  |
None | 0.655 | N | 0.478 | 0.185 | 0.243972157842 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| I/R | None | None | 0.794 | N | 0.499 | 0.349 | 0.761402108219 | gnomAD-4.0.0 | 6.84461E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99716E-07 | 0 | 0 |
| I/T | rs1444203818 |
-2.458 | 0.183 | N | 0.407 | 0.214 | 0.467161347466 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| I/T | rs1444203818 |
-2.458 | 0.183 | N | 0.407 | 0.214 | 0.467161347466 | gnomAD-4.0.0 | 1.64271E-05 | None | None | None | None | N | None | 0 | 2.23744E-05 | None | 0 | 0 | None | 0 | 0 | 1.97937E-05 | 1.1598E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6843 | likely_pathogenic | 0.6174 | pathogenic | -2.114 | Highly Destabilizing | 0.129 | N | 0.34 | neutral | None | None | None | None | N |
| I/C | 0.7704 | likely_pathogenic | 0.7618 | pathogenic | -1.148 | Destabilizing | 0.836 | D | 0.469 | neutral | None | None | None | None | N |
| I/D | 0.9804 | likely_pathogenic | 0.9797 | pathogenic | -2.575 | Highly Destabilizing | 0.836 | D | 0.516 | neutral | None | None | None | None | N |
| I/E | 0.944 | likely_pathogenic | 0.9374 | pathogenic | -2.3 | Highly Destabilizing | 0.418 | N | 0.489 | neutral | None | None | None | None | N |
| I/F | 0.5062 | ambiguous | 0.4053 | ambiguous | -1.228 | Destabilizing | 0.418 | N | 0.455 | neutral | None | None | None | None | N |
| I/G | 0.9164 | likely_pathogenic | 0.8823 | pathogenic | -2.689 | Highly Destabilizing | 0.418 | N | 0.457 | neutral | None | None | None | None | N |
| I/H | 0.9243 | likely_pathogenic | 0.9136 | pathogenic | -2.401 | Highly Destabilizing | 0.983 | D | 0.479 | neutral | None | None | None | None | N |
| I/K | 0.925 | likely_pathogenic | 0.9108 | pathogenic | -1.443 | Destabilizing | 0.351 | N | 0.489 | neutral | N | 0.486622203 | None | None | N |
| I/L | 0.1245 | likely_benign | 0.0919 | benign | -0.434 | Destabilizing | None | N | 0.098 | neutral | N | 0.466240223 | None | None | N |
| I/M | 0.1866 | likely_benign | 0.1484 | benign | -0.379 | Destabilizing | 0.655 | D | 0.478 | neutral | N | 0.48788965 | None | None | N |
| I/N | 0.7675 | likely_pathogenic | 0.757 | pathogenic | -1.938 | Destabilizing | 0.836 | D | 0.483 | neutral | None | None | None | None | N |
| I/P | 0.9516 | likely_pathogenic | 0.9507 | pathogenic | -0.977 | Destabilizing | 0.002 | N | 0.401 | neutral | None | None | None | None | N |
| I/Q | 0.8668 | likely_pathogenic | 0.8457 | pathogenic | -1.684 | Destabilizing | 0.836 | D | 0.491 | neutral | None | None | None | None | N |
| I/R | 0.8843 | likely_pathogenic | 0.8718 | pathogenic | -1.445 | Destabilizing | 0.794 | D | 0.499 | neutral | N | 0.486622203 | None | None | N |
| I/S | 0.7173 | likely_pathogenic | 0.6899 | pathogenic | -2.562 | Highly Destabilizing | 0.418 | N | 0.428 | neutral | None | None | None | None | N |
| I/T | 0.6977 | likely_pathogenic | 0.5976 | pathogenic | -2.132 | Highly Destabilizing | 0.183 | N | 0.407 | neutral | N | 0.486267596 | None | None | N |
| I/V | 0.0898 | likely_benign | 0.0801 | benign | -0.977 | Destabilizing | 0.001 | N | 0.125 | neutral | N | 0.438671224 | None | None | N |
| I/W | 0.9679 | likely_pathogenic | 0.9605 | pathogenic | -1.721 | Destabilizing | 0.983 | D | 0.517 | neutral | None | None | None | None | N |
| I/Y | 0.8939 | likely_pathogenic | 0.8801 | pathogenic | -1.335 | Destabilizing | 0.836 | D | 0.497 | 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.