Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6957 | 21094;21095;21096 | chr2:178724506;178724505;178724504 | chr2:179589233;179589232;179589231 |
| N2AB | 6640 | 20143;20144;20145 | chr2:178724506;178724505;178724504 | chr2:179589233;179589232;179589231 |
| N2A | 5713 | 17362;17363;17364 | chr2:178724506;178724505;178724504 | chr2:179589233;179589232;179589231 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 | 0.001 | N | 0.065 | 0.201 | 0.37550373646 | gnomAD-4.0.0 | 1.37525E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.03917E-07 | 0 | 1.66556E-05 |
| M/L | rs375262781  |
-0.148 | 0.065 | N | 0.107 | 0.212 | 0.478755181577 | gnomAD-2.1.1 | 2.16E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.94E-05 | 1.41924E-04 |
| M/L | rs375262781 |
-0.148 | 0.065 | N | 0.107 | 0.212 | 0.478755181577 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| M/L | rs375262781 |
-0.148 | 0.065 | N | 0.107 | 0.212 | 0.478755181577 | gnomAD-4.0.0 | 2.98795E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.91713E-05 | 0 | 3.21937E-05 |
| M/R | None | None | 0.975 | N | 0.429 | 0.395 | 0.696953486674 | gnomAD-4.0.0 | 1.60957E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.90274E-06 | 0 | 0 |
| M/T | rs754721444 |
-0.078 | 0.425 | N | 0.309 | 0.32 | None | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/T | rs754721444 |
-0.078 | 0.425 | N | 0.309 | 0.32 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | rs754721444 |
-0.078 | 0.425 | N | 0.309 | 0.32 | None | gnomAD-4.0.0 | 2.58602E-06 | None | None | None | None | N | None | 3.39432E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.2865 | likely_benign | 0.2677 | benign | -1.228 | Destabilizing | 0.3 | N | 0.295 | neutral | None | None | None | None | N |
| M/C | 0.7405 | likely_pathogenic | 0.7171 | pathogenic | -0.83 | Destabilizing | 0.981 | D | 0.349 | neutral | None | None | None | None | N |
| M/D | 0.7931 | likely_pathogenic | 0.809 | pathogenic | -0.162 | Destabilizing | 0.981 | D | 0.429 | neutral | None | None | None | None | N |
| M/E | 0.367 | ambiguous | 0.4068 | ambiguous | -0.177 | Destabilizing | 0.936 | D | 0.401 | neutral | None | None | None | None | N |
| M/F | 0.354 | ambiguous | 0.305 | benign | -0.522 | Destabilizing | 0.704 | D | 0.205 | neutral | None | None | None | None | N |
| M/G | 0.5433 | ambiguous | 0.5153 | ambiguous | -1.486 | Destabilizing | 0.936 | D | 0.37 | neutral | None | None | None | None | N |
| M/H | 0.4968 | ambiguous | 0.5138 | ambiguous | -0.636 | Destabilizing | 0.981 | D | 0.325 | neutral | None | None | None | None | N |
| M/I | 0.2481 | likely_benign | 0.24 | benign | -0.601 | Destabilizing | 0.001 | N | 0.065 | neutral | N | 0.42336899 | None | None | N |
| M/K | 0.1564 | likely_benign | 0.1897 | benign | -0.196 | Destabilizing | 0.784 | D | 0.319 | neutral | N | 0.445112486 | None | None | N |
| M/L | 0.1354 | likely_benign | 0.1209 | benign | -0.601 | Destabilizing | 0.065 | N | 0.107 | neutral | N | 0.411266484 | None | None | N |
| M/N | 0.5164 | ambiguous | 0.5265 | ambiguous | 0.01 | Stabilizing | 0.981 | D | 0.409 | neutral | None | None | None | None | N |
| M/P | 0.9342 | likely_pathogenic | 0.9071 | pathogenic | -0.782 | Destabilizing | 0.981 | D | 0.417 | neutral | None | None | None | None | N |
| M/Q | 0.182 | likely_benign | 0.2116 | benign | -0.122 | Destabilizing | 0.981 | D | 0.338 | neutral | None | None | None | None | N |
| M/R | 0.1627 | likely_benign | 0.189 | benign | 0.297 | Stabilizing | 0.975 | D | 0.429 | neutral | N | 0.437743796 | None | None | N |
| M/S | 0.3594 | ambiguous | 0.3474 | ambiguous | -0.532 | Destabilizing | 0.828 | D | 0.319 | neutral | None | None | None | None | N |
| M/T | 0.1517 | likely_benign | 0.1531 | benign | -0.44 | Destabilizing | 0.425 | N | 0.309 | neutral | N | 0.393779588 | None | None | N |
| M/V | 0.0701 | likely_benign | 0.067 | benign | -0.782 | Destabilizing | 0.003 | N | 0.063 | neutral | N | 0.396832962 | None | None | N |
| M/W | 0.7065 | likely_pathogenic | 0.6571 | pathogenic | -0.457 | Destabilizing | 0.995 | D | 0.346 | neutral | None | None | None | None | N |
| M/Y | 0.6277 | likely_pathogenic | 0.6012 | pathogenic | -0.421 | Destabilizing | 0.981 | D | 0.426 | 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.