Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29196 | 87811;87812;87813 | chr2:178557768;178557767;178557766 | chr2:179422495;179422494;179422493 |
| N2AB | 27555 | 82888;82889;82890 | chr2:178557768;178557767;178557766 | chr2:179422495;179422494;179422493 |
| N2A | 26628 | 80107;80108;80109 | chr2:178557768;178557767;178557766 | chr2:179422495;179422494;179422493 |
| N2B | 20131 | 60616;60617;60618 | chr2:178557768;178557767;178557766 | chr2:179422495;179422494;179422493 |
| Novex-1 | 20256 | 60991;60992;60993 | chr2:178557768;178557767;178557766 | chr2:179422495;179422494;179422493 |
| Novex-2 | 20323 | 61192;61193;61194 | chr2:178557768;178557767;178557766 | chr2:179422495;179422494;179422493 |
| 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 | None | None | None | N | 0.098 | 0.051 | 0.313818047136 | 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 |
| M/T | rs758449685  |
-1.274 | None | N | 0.161 | 0.098 | 0.159798565429 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| M/T | rs758449685 |
-1.274 | None | N | 0.161 | 0.098 | 0.159798565429 | gnomAD-4.0.0 | 1.59104E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43295E-05 | 0 |
| M/V | rs765797994 |
-1.465 | None | N | 0.085 | 0.059 | 0.279370189704 | gnomAD-2.1.1 | 2.81E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.21E-05 | 0 |
| M/V | rs765797994 |
-1.465 | None | N | 0.085 | 0.059 | 0.279370189704 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/V | rs765797994 |
-1.465 | None | N | 0.085 | 0.059 | 0.279370189704 | gnomAD-4.0.0 | 8.05519E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.56177E-05 | 0 | 9.32319E-06 | 0 | 1.60097E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.1325 | likely_benign | 0.1433 | benign | -1.736 | Destabilizing | 0.002 | N | 0.249 | neutral | None | None | None | None | N |
| M/C | 0.4355 | ambiguous | 0.4276 | ambiguous | -1.043 | Destabilizing | 0.245 | N | 0.433 | neutral | None | None | None | None | N |
| M/D | 0.6335 | likely_pathogenic | 0.6993 | pathogenic | -0.518 | Destabilizing | 0.018 | N | 0.443 | neutral | None | None | None | None | N |
| M/E | 0.2916 | likely_benign | 0.3488 | ambiguous | -0.486 | Destabilizing | 0.018 | N | 0.378 | neutral | None | None | None | None | N |
| M/F | 0.2509 | likely_benign | 0.2716 | benign | -0.702 | Destabilizing | 0.018 | N | 0.317 | neutral | None | None | None | None | N |
| M/G | 0.3075 | likely_benign | 0.3321 | benign | -2.039 | Highly Destabilizing | 0.018 | N | 0.37 | neutral | None | None | None | None | N |
| M/H | 0.3283 | likely_benign | 0.3367 | benign | -1.043 | Destabilizing | 0.497 | N | 0.508 | neutral | None | None | None | None | N |
| M/I | 0.1684 | likely_benign | 0.1851 | benign | -0.949 | Destabilizing | None | N | 0.098 | neutral | N | 0.406041517 | None | None | N |
| M/K | 0.1608 | likely_benign | 0.1788 | benign | -0.629 | Destabilizing | 0.014 | N | 0.37 | neutral | N | 0.393053577 | None | None | N |
| M/L | 0.1105 | likely_benign | 0.1162 | benign | -0.949 | Destabilizing | None | N | 0.083 | neutral | N | 0.409639183 | None | None | N |
| M/N | 0.2203 | likely_benign | 0.2438 | benign | -0.469 | Destabilizing | 0.018 | N | 0.477 | neutral | None | None | None | None | N |
| M/P | 0.9046 | likely_pathogenic | 0.9154 | pathogenic | -1.186 | Destabilizing | None | N | 0.297 | neutral | None | None | None | None | N |
| M/Q | 0.1566 | likely_benign | 0.167 | benign | -0.545 | Destabilizing | 0.085 | N | 0.325 | neutral | None | None | None | None | N |
| M/R | 0.1782 | likely_benign | 0.2083 | benign | -0.104 | Destabilizing | 0.033 | N | 0.446 | neutral | N | 0.382143151 | None | None | N |
| M/S | 0.1276 | likely_benign | 0.1356 | benign | -1.059 | Destabilizing | 0.004 | N | 0.294 | neutral | None | None | None | None | N |
| M/T | 0.0622 | likely_benign | 0.0655 | benign | -0.922 | Destabilizing | None | N | 0.161 | neutral | N | 0.281709584 | None | None | N |
| M/V | 0.0577 | likely_benign | 0.0622 | benign | -1.186 | Destabilizing | None | N | 0.085 | neutral | N | 0.413506208 | None | None | N |
| M/W | 0.5295 | ambiguous | 0.5612 | ambiguous | -0.631 | Destabilizing | 0.497 | N | 0.438 | neutral | None | None | None | None | N |
| M/Y | 0.4573 | ambiguous | 0.4756 | ambiguous | -0.683 | Destabilizing | 0.085 | N | 0.457 | 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.