Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7544 | 22855;22856;22857 | chr2:178722033;178722032;178722031 | chr2:179586760;179586759;179586758 |
| N2AB | 7227 | 21904;21905;21906 | chr2:178722033;178722032;178722031 | chr2:179586760;179586759;179586758 |
| N2A | 6300 | 19123;19124;19125 | chr2:178722033;178722032;178722031 | chr2:179586760;179586759;179586758 |
| 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/K | None | None | 0.006 | D | 0.205 | 0.356 | 0.655352004 | gnomAD-4.0.0 | 1.36872E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79927E-06 | 0 | 0 |
| M/L | rs2078457617  |
None | None | N | 0.075 | 0.227 | 0.546824882953 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 2.61917E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/L | rs2078457617 |
None | None | N | 0.075 | 0.227 | 0.546824882953 | gnomAD-4.0.0 | 3.71886E-06 | None | None | None | None | I | None | 0 | 6.66778E-05 | None | 0 | 0 | None | 1.56216E-05 | 0 | 8.47756E-07 | 0 | 0 |
| M/T | rs1234192175 |
None | 0.302 | N | 0.428 | 0.32 | 0.801681314988 | gnomAD-4.0.0 | 6.8436E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99635E-07 | 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 | 0.6216 | likely_pathogenic | 0.6128 | pathogenic | -2.043 | Highly Destabilizing | 0.2 | N | 0.34 | neutral | None | None | None | None | I |
| M/C | 0.9145 | likely_pathogenic | 0.9077 | pathogenic | -1.444 | Destabilizing | 0.968 | D | 0.53 | neutral | None | None | None | None | I |
| M/D | 0.9747 | likely_pathogenic | 0.9767 | pathogenic | -1.408 | Destabilizing | 0.738 | D | 0.543 | neutral | None | None | None | None | I |
| M/E | 0.8279 | likely_pathogenic | 0.8403 | pathogenic | -1.373 | Destabilizing | 0.365 | N | 0.433 | neutral | None | None | None | None | I |
| M/F | 0.4544 | ambiguous | 0.4624 | ambiguous | -1.106 | Destabilizing | 0.365 | N | 0.391 | neutral | None | None | None | None | I |
| M/G | 0.8639 | likely_pathogenic | 0.8658 | pathogenic | -2.357 | Highly Destabilizing | 0.538 | D | 0.467 | neutral | None | None | None | None | I |
| M/H | 0.8882 | likely_pathogenic | 0.8986 | pathogenic | -1.578 | Destabilizing | 0.968 | D | 0.551 | neutral | None | None | None | None | I |
| M/I | 0.2112 | likely_benign | 0.2143 | benign | -1.212 | Destabilizing | None | N | 0.08 | neutral | N | 0.451710384 | None | None | I |
| M/K | 0.6217 | likely_pathogenic | 0.6544 | pathogenic | -0.938 | Destabilizing | 0.006 | N | 0.205 | neutral | D | 0.522090402 | None | None | I |
| M/L | 0.1115 | likely_benign | 0.121 | benign | -1.212 | Destabilizing | None | N | 0.075 | neutral | N | 0.412189204 | None | None | I |
| M/N | 0.8588 | likely_pathogenic | 0.8726 | pathogenic | -0.803 | Destabilizing | 0.738 | D | 0.531 | neutral | None | None | None | None | I |
| M/P | 0.7968 | likely_pathogenic | 0.7876 | pathogenic | -1.465 | Destabilizing | 0.896 | D | 0.537 | neutral | None | None | None | None | I |
| M/Q | 0.5775 | likely_pathogenic | 0.6063 | pathogenic | -0.915 | Destabilizing | 0.582 | D | 0.451 | neutral | None | None | None | None | I |
| M/R | 0.6268 | likely_pathogenic | 0.6609 | pathogenic | -0.494 | Destabilizing | 0.178 | N | 0.471 | neutral | D | 0.522783835 | None | None | I |
| M/S | 0.7208 | likely_pathogenic | 0.7399 | pathogenic | -1.344 | Destabilizing | 0.365 | N | 0.453 | neutral | None | None | None | None | I |
| M/T | 0.4766 | ambiguous | 0.51 | ambiguous | -1.21 | Destabilizing | 0.302 | N | 0.428 | neutral | N | 0.463178171 | None | None | I |
| M/V | 0.0824 | likely_benign | 0.078 | benign | -1.465 | Destabilizing | 0.039 | N | 0.186 | neutral | N | 0.471912298 | None | None | I |
| M/W | 0.8494 | likely_pathogenic | 0.8673 | pathogenic | -1.09 | Destabilizing | 0.991 | D | 0.521 | neutral | None | None | None | None | I |
| M/Y | 0.8212 | likely_pathogenic | 0.8338 | pathogenic | -1.115 | Destabilizing | 0.896 | D | 0.529 | neutral | None | None | None | None | I |
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.