Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20261 | 61006;61007;61008 | chr2:178590944;178590943;178590942 | chr2:179455671;179455670;179455669 |
| N2AB | 18620 | 56083;56084;56085 | chr2:178590944;178590943;178590942 | chr2:179455671;179455670;179455669 |
| N2A | 17693 | 53302;53303;53304 | chr2:178590944;178590943;178590942 | chr2:179455671;179455670;179455669 |
| N2B | 11196 | 33811;33812;33813 | chr2:178590944;178590943;178590942 | chr2:179455671;179455670;179455669 |
| Novex-1 | 11321 | 34186;34187;34188 | chr2:178590944;178590943;178590942 | chr2:179455671;179455670;179455669 |
| Novex-2 | 11388 | 34387;34388;34389 | chr2:178590944;178590943;178590942 | chr2:179455671;179455670;179455669 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs555901678  |
0.392 | None | N | 0.427 | 0.126 | 0.0401082797425 | gnomAD-2.1.1 | 7.16E-06 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.85E-06 | 0 |
| T/I | rs555901678 |
0.392 | None | N | 0.427 | 0.126 | 0.0401082797425 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs555901678 |
0.392 | None | N | 0.427 | 0.126 | 0.0401082797425 | gnomAD-4.0.0 | 1.7356E-05 | None | None | None | None | N | None | 1.86936E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 1.10214E-05 | 0 | 1.60138E-05 |
| T/K | rs555901678 |
-0.335 | None | N | 0.422 | 0.142 | 0.0297737177859 | gnomAD-2.1.1 | 5.65E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 4.24975E-04 | None | 0 | 0 | 1.665E-04 |
| T/K | rs555901678 |
-0.335 | None | N | 0.422 | 0.142 | 0.0297737177859 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 6.21375E-04 | 0 |
| T/K | rs555901678 |
-0.335 | None | N | 0.422 | 0.142 | 0.0297737177859 | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 2E-03 | None |
| T/K | rs555901678 |
-0.335 | None | N | 0.422 | 0.142 | 0.0297737177859 | gnomAD-4.0.0 | 1.92142E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.40457E-04 | 0 |
| T/P | rs1343412391 |
None | 0.031 | N | 0.673 | 0.027 | 0.0806252709748 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/P | rs1343412391 |
None | 0.031 | N | 0.673 | 0.027 | 0.0806252709748 | gnomAD-4.0.0 | 6.5773E-06 | None | None | None | None | N | None | 2.41313E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/S | rs1343412391 |
-0.892 | 0.001 | N | 0.417 | 0.023 | 0.0297737177859 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0586 | likely_benign | 0.0572 | benign | -0.25 | Destabilizing | None | N | 0.182 | neutral | N | 0.377177261 | None | None | N |
| T/C | 0.2574 | likely_benign | 0.2342 | benign | -0.305 | Destabilizing | 0.131 | N | 0.585 | neutral | None | None | None | None | N |
| T/D | 0.2083 | likely_benign | 0.188 | benign | 0.394 | Stabilizing | 0.004 | N | 0.54 | neutral | None | None | None | None | N |
| T/E | 0.1296 | likely_benign | 0.1197 | benign | 0.336 | Stabilizing | None | N | 0.416 | neutral | None | None | None | None | N |
| T/F | 0.1412 | likely_benign | 0.1309 | benign | -0.717 | Destabilizing | 0.021 | N | 0.756 | deleterious | None | None | None | None | N |
| T/G | 0.175 | likely_benign | 0.1527 | benign | -0.391 | Destabilizing | 0.004 | N | 0.577 | neutral | None | None | None | None | N |
| T/H | 0.1576 | likely_benign | 0.1524 | benign | -0.592 | Destabilizing | 0.131 | N | 0.651 | prob.neutral | None | None | None | None | N |
| T/I | 0.0641 | likely_benign | 0.0586 | benign | None | Stabilizing | None | N | 0.427 | neutral | N | 0.453715247 | None | None | N |
| T/K | 0.0878 | likely_benign | 0.089 | benign | -0.244 | Destabilizing | None | N | 0.422 | neutral | N | 0.359015575 | None | None | N |
| T/L | 0.0534 | likely_benign | 0.0513 | benign | None | Stabilizing | 0.001 | N | 0.571 | neutral | None | None | None | None | N |
| T/M | 0.0663 | likely_benign | 0.064 | benign | -0.047 | Destabilizing | 0.069 | N | 0.641 | neutral | None | None | None | None | N |
| T/N | 0.0908 | likely_benign | 0.0819 | benign | -0.113 | Destabilizing | 0.021 | N | 0.423 | neutral | None | None | None | None | N |
| T/P | 0.0584 | likely_benign | 0.0588 | benign | -0.054 | Destabilizing | 0.031 | N | 0.673 | prob.neutral | N | 0.412001911 | None | None | N |
| T/Q | 0.1201 | likely_benign | 0.1166 | benign | -0.264 | Destabilizing | None | N | 0.443 | neutral | None | None | None | None | N |
| T/R | 0.1018 | likely_benign | 0.1069 | benign | -0.016 | Destabilizing | 0.003 | N | 0.565 | neutral | N | 0.461257295 | None | None | N |
| T/S | 0.0845 | likely_benign | 0.078 | benign | -0.337 | Destabilizing | 0.001 | N | 0.417 | neutral | N | 0.390626561 | None | None | N |
| T/V | 0.062 | likely_benign | 0.0555 | benign | -0.054 | Destabilizing | None | N | 0.257 | neutral | None | None | None | None | N |
| T/W | 0.4577 | ambiguous | 0.4566 | ambiguous | -0.762 | Destabilizing | 0.633 | D | 0.672 | prob.neutral | None | None | None | None | N |
| T/Y | 0.1812 | likely_benign | 0.1715 | benign | -0.447 | Destabilizing | 0.131 | N | 0.751 | deleterious | 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.