Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27022 | 81289;81290;81291 | chr2:178565068;178565067;178565066 | chr2:179429795;179429794;179429793 |
| N2AB | 25381 | 76366;76367;76368 | chr2:178565068;178565067;178565066 | chr2:179429795;179429794;179429793 |
| N2A | 24454 | 73585;73586;73587 | chr2:178565068;178565067;178565066 | chr2:179429795;179429794;179429793 |
| N2B | 17957 | 54094;54095;54096 | chr2:178565068;178565067;178565066 | chr2:179429795;179429794;179429793 |
| Novex-1 | 18082 | 54469;54470;54471 | chr2:178565068;178565067;178565066 | chr2:179429795;179429794;179429793 |
| Novex-2 | 18149 | 54670;54671;54672 | chr2:178565068;178565067;178565066 | chr2:179429795;179429794;179429793 |
| 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 | 0.115 | 0.08 | 0.224531998449 | gnomAD-4.0.0 | 1.59161E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43336E-05 | 0 |
| M/L | rs1300719921  |
-0.689 | 0.003 | N | 0.107 | 0.034 | 0.428747304603 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| M/L | rs1300719921 |
-0.689 | 0.003 | N | 0.107 | 0.034 | 0.428747304603 | gnomAD-4.0.0 | 6.84268E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99544E-07 | 0 | 0 |
| M/T | None | None | None | N | 0.181 | 0.081 | 0.465038187318 | gnomAD-4.0.0 | 2.05279E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69862E-06 | 0 | 0 |
| M/V | rs1300719921 |
None | None | N | 0.116 | 0.051 | 0.242825505644 | 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/V | rs1300719921 |
None | None | N | 0.116 | 0.051 | 0.242825505644 | gnomAD-4.0.0 | 4.33822E-06 | None | None | None | None | N | None | 1.33479E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.08608E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.242 | likely_benign | 0.2142 | benign | -1.14 | Destabilizing | 0.025 | N | 0.269 | neutral | None | None | None | None | N |
| M/C | 0.532 | ambiguous | 0.5546 | ambiguous | -0.859 | Destabilizing | 0.859 | D | 0.466 | neutral | None | None | None | None | N |
| M/D | 0.7701 | likely_pathogenic | 0.7578 | pathogenic | -0.128 | Destabilizing | 0.22 | N | 0.539 | neutral | None | None | None | None | N |
| M/E | 0.4637 | ambiguous | 0.4347 | ambiguous | -0.147 | Destabilizing | 0.22 | N | 0.477 | neutral | None | None | None | None | N |
| M/F | 0.3959 | ambiguous | 0.3644 | ambiguous | -0.436 | Destabilizing | 0.22 | N | 0.297 | neutral | None | None | None | None | N |
| M/G | 0.55 | ambiguous | 0.5027 | ambiguous | -1.388 | Destabilizing | 0.22 | N | 0.487 | neutral | None | None | None | None | N |
| M/H | 0.5024 | ambiguous | 0.4859 | ambiguous | -0.437 | Destabilizing | 0.859 | D | 0.507 | neutral | None | None | None | None | N |
| M/I | 0.1458 | likely_benign | 0.1312 | benign | -0.548 | Destabilizing | None | N | 0.115 | neutral | N | 0.432612043 | None | None | N |
| M/K | 0.25 | likely_benign | 0.2366 | benign | -0.117 | Destabilizing | 0.175 | N | 0.422 | neutral | N | 0.42295241 | None | None | N |
| M/L | 0.1159 | likely_benign | 0.1009 | benign | -0.548 | Destabilizing | 0.003 | N | 0.107 | neutral | N | 0.457662416 | None | None | N |
| M/N | 0.373 | ambiguous | 0.3399 | benign | 0.047 | Stabilizing | 0.22 | N | 0.579 | neutral | None | None | None | None | N |
| M/P | 0.3611 | ambiguous | 0.3287 | benign | -0.717 | Destabilizing | 0.364 | N | 0.579 | neutral | None | None | None | None | N |
| M/Q | 0.2501 | likely_benign | 0.2542 | benign | -0.104 | Destabilizing | 0.364 | N | 0.373 | neutral | None | None | None | None | N |
| M/R | 0.2794 | likely_benign | 0.2629 | benign | 0.435 | Stabilizing | 0.175 | N | 0.509 | neutral | N | 0.426376717 | None | None | N |
| M/S | 0.3006 | likely_benign | 0.276 | benign | -0.497 | Destabilizing | 0.055 | N | 0.403 | neutral | None | None | None | None | N |
| M/T | 0.1097 | likely_benign | 0.0941 | benign | -0.411 | Destabilizing | None | N | 0.181 | neutral | N | 0.355649983 | None | None | N |
| M/V | 0.0569 | likely_benign | 0.0565 | benign | -0.717 | Destabilizing | None | N | 0.116 | neutral | N | 0.406617521 | None | None | N |
| M/W | 0.7316 | likely_pathogenic | 0.706 | pathogenic | -0.359 | Destabilizing | 0.958 | D | 0.45 | neutral | None | None | None | None | N |
| M/Y | 0.6464 | likely_pathogenic | 0.6074 | pathogenic | -0.32 | Destabilizing | 0.364 | N | 0.531 | 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.