Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18719 | 56380;56381;56382 | chr2:178599746;178599745;178599744 | chr2:179464473;179464472;179464471 |
| N2AB | 17078 | 51457;51458;51459 | chr2:178599746;178599745;178599744 | chr2:179464473;179464472;179464471 |
| N2A | 16151 | 48676;48677;48678 | chr2:178599746;178599745;178599744 | chr2:179464473;179464472;179464471 |
| N2B | 9654 | 29185;29186;29187 | chr2:178599746;178599745;178599744 | chr2:179464473;179464472;179464471 |
| Novex-1 | 9779 | 29560;29561;29562 | chr2:178599746;178599745;178599744 | chr2:179464473;179464472;179464471 |
| Novex-2 | 9846 | 29761;29762;29763 | chr2:178599746;178599745;178599744 | chr2:179464473;179464472;179464471 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs1038577765  |
None | 0.002 | N | 0.241 | 0.169 | 0.264547087235 | 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 |
| F/Y | rs750817310 |
-0.754 | 0.642 | N | 0.45 | 0.129 | 0.370789594751 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| F/Y | rs750817310 |
-0.754 | 0.642 | N | 0.45 | 0.129 | 0.370789594751 | gnomAD-4.0.0 | 8.40225E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.18751E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.4064 | ambiguous | 0.3864 | ambiguous | -2.41 | Highly Destabilizing | 0.329 | N | 0.459 | neutral | None | None | None | None | N |
| F/C | 0.1915 | likely_benign | 0.1868 | benign | -1.172 | Destabilizing | 0.993 | D | 0.565 | neutral | N | 0.459329873 | None | None | N |
| F/D | 0.6148 | likely_pathogenic | 0.5349 | ambiguous | -1.327 | Destabilizing | 0.543 | D | 0.539 | neutral | None | None | None | None | N |
| F/E | 0.466 | ambiguous | 0.4006 | ambiguous | -1.24 | Destabilizing | 0.007 | N | 0.421 | neutral | None | None | None | None | N |
| F/G | 0.6821 | likely_pathogenic | 0.6335 | pathogenic | -2.755 | Highly Destabilizing | 0.704 | D | 0.541 | neutral | None | None | None | None | N |
| F/H | 0.2411 | likely_benign | 0.2178 | benign | -0.99 | Destabilizing | 0.003 | N | 0.245 | neutral | None | None | None | None | N |
| F/I | 0.1406 | likely_benign | 0.1357 | benign | -1.362 | Destabilizing | 0.27 | N | 0.419 | neutral | N | 0.46888977 | None | None | N |
| F/K | 0.5209 | ambiguous | 0.4515 | ambiguous | -1.262 | Destabilizing | 0.543 | D | 0.536 | neutral | None | None | None | None | N |
| F/L | 0.5182 | ambiguous | 0.5073 | ambiguous | -1.362 | Destabilizing | 0.002 | N | 0.241 | neutral | N | 0.413476417 | None | None | N |
| F/M | 0.2566 | likely_benign | 0.2478 | benign | -0.991 | Destabilizing | 0.893 | D | 0.501 | neutral | None | None | None | None | N |
| F/N | 0.3543 | ambiguous | 0.3219 | benign | -1.28 | Destabilizing | 0.704 | D | 0.539 | neutral | None | None | None | None | N |
| F/P | 0.9961 | likely_pathogenic | 0.994 | pathogenic | -1.707 | Destabilizing | 0.944 | D | 0.6 | neutral | None | None | None | None | N |
| F/Q | 0.332 | likely_benign | 0.3058 | benign | -1.411 | Destabilizing | 0.085 | N | 0.445 | neutral | None | None | None | None | N |
| F/R | 0.4721 | ambiguous | 0.4009 | ambiguous | -0.541 | Destabilizing | 0.704 | D | 0.565 | neutral | None | None | None | None | N |
| F/S | 0.2615 | likely_benign | 0.2269 | benign | -2.084 | Highly Destabilizing | 0.425 | N | 0.509 | neutral | N | 0.44051109 | None | None | N |
| F/T | 0.2921 | likely_benign | 0.2677 | benign | -1.905 | Destabilizing | 0.704 | D | 0.539 | neutral | None | None | None | None | N |
| F/V | 0.1377 | likely_benign | 0.1324 | benign | -1.707 | Destabilizing | 0.006 | N | 0.24 | neutral | N | 0.463771951 | None | None | N |
| F/W | 0.3601 | ambiguous | 0.3115 | benign | -0.46 | Destabilizing | 0.995 | D | 0.546 | neutral | None | None | None | None | N |
| F/Y | 0.0992 | likely_benign | 0.0914 | benign | -0.682 | Destabilizing | 0.642 | D | 0.45 | neutral | N | 0.389964839 | 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.