Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4989 | 15190;15191;15192 | chr2:178734959;178734958;178734957 | chr2:179599686;179599685;179599684 |
| N2AB | 4672 | 14239;14240;14241 | chr2:178734959;178734958;178734957 | chr2:179599686;179599685;179599684 |
| N2A | 3745 | 11458;11459;11460 | chr2:178734959;178734958;178734957 | chr2:179599686;179599685;179599684 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs1560844298  |
None | 1.0 | N | 0.757 | 0.372 | 0.504297271243 | gnomAD-4.0.0 | 3.26883E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.94149E-06 | 0 | 3.07598E-05 |
| P/S | rs80003323 |
-0.194 | 1.0 | N | 0.739 | 0.321 | 0.144782658237 | gnomAD-2.1.1 | 4.47E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.01E-05 | 0 |
| P/S | rs80003323 |
-0.194 | 1.0 | N | 0.739 | 0.321 | 0.144782658237 | 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 |
| P/S | rs80003323 |
-0.194 | 1.0 | N | 0.739 | 0.321 | 0.144782658237 | gnomAD-4.0.0 | 6.26231E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.54791E-06 | 0 | 0 |
| P/T | rs80003323 |
-0.209 | 1.0 | N | 0.724 | 0.327 | None | gnomAD-2.1.1 | 4.47E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.01E-05 | 0 |
| P/T | rs80003323 |
-0.209 | 1.0 | N | 0.724 | 0.327 | None | 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 |
| P/T | rs80003323 |
-0.209 | 1.0 | N | 0.724 | 0.327 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| P/T | rs80003323 |
-0.209 | 1.0 | N | 0.724 | 0.327 | None | gnomAD-4.0.0 | 1.00189E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.66113E-04 | 1.11124E-05 | 0 | 3.22956E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1002 | likely_benign | 0.1385 | benign | -0.52 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | N | 0.448508167 | None | None | N |
| P/C | 0.689 | likely_pathogenic | 0.811 | pathogenic | -0.574 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| P/D | 0.5878 | likely_pathogenic | 0.7734 | pathogenic | -0.02 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| P/E | 0.4131 | ambiguous | 0.6262 | pathogenic | -0.12 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| P/F | 0.6304 | likely_pathogenic | 0.7923 | pathogenic | -0.668 | Destabilizing | 1.0 | D | 0.7 | prob.neutral | None | None | None | None | N |
| P/G | 0.4203 | ambiguous | 0.5603 | ambiguous | -0.672 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| P/H | 0.2607 | likely_benign | 0.3881 | ambiguous | -0.193 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | N | 0.4326421 | None | None | N |
| P/I | 0.4525 | ambiguous | 0.6194 | pathogenic | -0.265 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| P/K | 0.4337 | ambiguous | 0.6372 | pathogenic | -0.343 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | N |
| P/L | 0.1872 | likely_benign | 0.2699 | benign | -0.265 | Destabilizing | 1.0 | D | 0.757 | deleterious | N | 0.453786333 | None | None | N |
| P/M | 0.4514 | ambiguous | 0.5966 | pathogenic | -0.325 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| P/N | 0.4078 | ambiguous | 0.5813 | pathogenic | -0.073 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| P/Q | 0.214 | likely_benign | 0.3426 | ambiguous | -0.288 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| P/R | 0.2585 | likely_benign | 0.405 | ambiguous | 0.138 | Stabilizing | 1.0 | D | 0.739 | prob.delet. | N | 0.442236816 | None | None | N |
| P/S | 0.1446 | likely_benign | 0.216 | benign | -0.502 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | N | 0.423040491 | None | None | N |
| P/T | 0.1344 | likely_benign | 0.2065 | benign | -0.494 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | N | 0.445315147 | None | None | N |
| P/V | 0.2986 | likely_benign | 0.4353 | ambiguous | -0.314 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| P/W | 0.8304 | likely_pathogenic | 0.9135 | pathogenic | -0.743 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| P/Y | 0.6193 | likely_pathogenic | 0.7707 | pathogenic | -0.44 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | 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.