Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3990 | 12193;12194;12195 | chr2:178741265;178741264;178741263 | chr2:179605992;179605991;179605990 |
| N2AB | 3673 | 11242;11243;11244 | chr2:178741265;178741264;178741263 | chr2:179605992;179605991;179605990 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3627 | 11104;11105;11106 | chr2:178741265;178741264;178741263 | chr2:179605992;179605991;179605990 |
| Novex-1 | 3752 | 11479;11480;11481 | chr2:178741265;178741264;178741263 | chr2:179605992;179605991;179605990 |
| Novex-2 | 3819 | 11680;11681;11682 | chr2:178741265;178741264;178741263 | chr2:179605992;179605991;179605990 |
| 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/H | rs33971253  |
None | 0.965 | N | 0.435 | 0.236 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/H | rs33971253 |
None | 0.965 | N | 0.435 | 0.236 | None | gnomAD-4.0.0 | 1.2394E-06 | None | None | None | None | I | None | 1.33472E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60113E-05 |
| P/L | rs33971253 |
0.129 | 0.338 | N | 0.457 | 0.236 | None | gnomAD-2.1.1 | 6.42171E-03 | None | None | None | None | I | None | 2.64988E-03 | 3.19751E-03 | None | 3.96825E-03 | 0 | None | 5.55556E-04 | None | 2.88485E-03 | 1.13901E-02 | 4.77528E-03 |
| P/L | rs33971253 |
0.129 | 0.338 | N | 0.457 | 0.236 | None | gnomAD-3.1.2 | 6.40074E-03 | None | None | None | None | I | None | 2.46092E-03 | 2.81745E-03 | 0 | 2.88184E-03 | 0 | None | 2.07234E-03 | 0 | 1.14508E-02 | 1.44867E-03 | 5.25813E-03 |
| P/L | rs33971253 |
0.129 | 0.338 | N | 0.457 | 0.236 | None | 1000 genomes | 2.79553E-03 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1.29E-02 | None | None | None | 1E-03 | None |
| P/L | rs33971253 |
0.129 | 0.338 | N | 0.457 | 0.236 | None | gnomAD-4.0.0 | 1.00365E-02 | None | None | None | None | I | None | 2.29199E-03 | 2.98343E-03 | None | 4.02E-03 | 0 | None | 3.66083E-03 | 4.94886E-04 | 1.26323E-02 | 5.5991E-04 | 8.56301E-03 |
| P/T | None | None | 0.003 | N | 0.304 | 0.087 | None | gnomAD-4.0.0 | 1.59127E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43279E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0869 | likely_benign | 0.0861 | benign | -0.118 | Destabilizing | 0.174 | N | 0.453 | neutral | N | 0.447752886 | None | None | I |
| P/C | 0.486 | ambiguous | 0.4021 | ambiguous | -0.333 | Destabilizing | 0.973 | D | 0.523 | neutral | None | None | None | None | I |
| P/D | 0.3058 | likely_benign | 0.2755 | benign | -0.317 | Destabilizing | 0.575 | D | 0.373 | neutral | None | None | None | None | I |
| P/E | 0.2033 | likely_benign | 0.1926 | benign | -0.458 | Destabilizing | 0.404 | N | 0.413 | neutral | None | None | None | None | I |
| P/F | 0.5005 | ambiguous | 0.4231 | ambiguous | -0.646 | Destabilizing | 0.906 | D | 0.476 | neutral | None | None | None | None | I |
| P/G | 0.2946 | likely_benign | 0.2595 | benign | -0.182 | Destabilizing | 0.404 | N | 0.435 | neutral | None | None | None | None | I |
| P/H | 0.1677 | likely_benign | 0.1487 | benign | 0.076 | Stabilizing | 0.965 | D | 0.435 | neutral | N | 0.497201256 | None | None | I |
| P/I | 0.2948 | likely_benign | 0.2581 | benign | -0.108 | Destabilizing | 0.704 | D | 0.476 | neutral | None | None | None | None | I |
| P/K | 0.2258 | likely_benign | 0.209 | benign | -0.098 | Destabilizing | 0.404 | N | 0.394 | neutral | None | None | None | None | I |
| P/L | 0.1287 | likely_benign | 0.1382 | benign | -0.108 | Destabilizing | 0.338 | N | 0.457 | neutral | N | 0.484141539 | None | None | I |
| P/M | 0.3033 | likely_benign | 0.2702 | benign | -0.175 | Destabilizing | 0.973 | D | 0.431 | neutral | None | None | None | None | I |
| P/N | 0.2801 | likely_benign | 0.2543 | benign | 0.247 | Stabilizing | 0.704 | D | 0.397 | neutral | None | None | None | None | I |
| P/Q | 0.127 | likely_benign | 0.1232 | benign | -0.031 | Destabilizing | 0.04 | N | 0.393 | neutral | None | None | None | None | I |
| P/R | 0.1466 | likely_benign | 0.1305 | benign | 0.37 | Stabilizing | 0.642 | D | 0.425 | neutral | N | 0.435167987 | None | None | I |
| P/S | 0.1099 | likely_benign | 0.1031 | benign | -0.012 | Destabilizing | 0.003 | N | 0.3 | neutral | N | 0.423606685 | None | None | I |
| P/T | 0.0885 | likely_benign | 0.0862 | benign | -0.065 | Destabilizing | 0.003 | N | 0.304 | neutral | N | 0.461243714 | None | None | I |
| P/V | 0.2252 | likely_benign | 0.2035 | benign | -0.081 | Destabilizing | 0.704 | D | 0.387 | neutral | None | None | None | None | I |
| P/W | 0.6116 | likely_pathogenic | 0.5124 | ambiguous | -0.737 | Destabilizing | 0.991 | D | 0.601 | neutral | None | None | None | None | I |
| P/Y | 0.4362 | ambiguous | 0.3628 | ambiguous | -0.403 | Destabilizing | 0.906 | D | 0.477 | 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.