Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2967 | 9124;9125;9126 | chr2:178769682;178769681;178769680 | chr2:179634409;179634408;179634407 |
| N2AB | 2967 | 9124;9125;9126 | chr2:178769682;178769681;178769680 | chr2:179634409;179634408;179634407 |
| N2A | 2967 | 9124;9125;9126 | chr2:178769682;178769681;178769680 | chr2:179634409;179634408;179634407 |
| N2B | 2921 | 8986;8987;8988 | chr2:178769682;178769681;178769680 | chr2:179634409;179634408;179634407 |
| Novex-1 | 2921 | 8986;8987;8988 | chr2:178769682;178769681;178769680 | chr2:179634409;179634408;179634407 |
| Novex-2 | 2921 | 8986;8987;8988 | chr2:178769682;178769681;178769680 | chr2:179634409;179634408;179634407 |
| Novex-3 | 2967 | 9124;9125;9126 | chr2:178769682;178769681;178769680 | chr2:179634409;179634408;179634407 |
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/A | rs1287851348  |
-0.965 | 0.139 | N | 0.13 | 0.316 | 0.309530620856 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| T/A | rs1287851348 |
-0.965 | 0.139 | N | 0.13 | 0.316 | 0.309530620856 | gnomAD-4.0.0 | 1.59186E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85866E-06 | 0 | 0 |
| T/I | rs764554139 |
0.159 | 0.784 | N | 0.379 | 0.256 | 0.55046033382 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/I | rs764554139 |
0.159 | 0.784 | N | 0.379 | 0.256 | 0.55046033382 | gnomAD-4.0.0 | 8.21399E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.39166E-04 | 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 | 0.1007 | likely_benign | 0.1049 | benign | -0.473 | Destabilizing | 0.139 | N | 0.13 | neutral | N | 0.514591404 | None | None | N |
| T/C | 0.4631 | ambiguous | 0.4919 | ambiguous | -0.398 | Destabilizing | 0.995 | D | 0.27 | neutral | None | None | None | None | N |
| T/D | 0.4434 | ambiguous | 0.4939 | ambiguous | -0.179 | Destabilizing | 0.329 | N | 0.257 | neutral | None | None | None | None | N |
| T/E | 0.285 | likely_benign | 0.3151 | benign | -0.211 | Destabilizing | 0.329 | N | 0.259 | neutral | None | None | None | None | N |
| T/F | 0.2682 | likely_benign | 0.2654 | benign | -0.579 | Destabilizing | 0.981 | D | 0.315 | neutral | None | None | None | None | N |
| T/G | 0.4144 | ambiguous | 0.4473 | ambiguous | -0.693 | Destabilizing | 0.495 | N | 0.205 | neutral | None | None | None | None | N |
| T/H | 0.1948 | likely_benign | 0.2144 | benign | -0.946 | Destabilizing | 0.944 | D | 0.299 | neutral | None | None | None | None | N |
| T/I | 0.1359 | likely_benign | 0.1474 | benign | 0.008 | Stabilizing | 0.784 | D | 0.379 | neutral | N | 0.502193171 | None | None | N |
| T/K | 0.1021 | likely_benign | 0.1217 | benign | -0.739 | Destabilizing | 0.003 | N | 0.12 | neutral | None | None | None | None | N |
| T/L | 0.1033 | likely_benign | 0.1059 | benign | 0.008 | Stabilizing | 0.495 | N | 0.266 | neutral | None | None | None | None | N |
| T/M | 0.0825 | likely_benign | 0.0847 | benign | 0.125 | Stabilizing | 0.981 | D | 0.279 | neutral | None | None | None | None | N |
| T/N | 0.1171 | likely_benign | 0.1364 | benign | -0.554 | Destabilizing | 0.01 | N | 0.107 | neutral | N | 0.516673248 | None | None | N |
| T/P | 0.3762 | ambiguous | 0.3736 | ambiguous | -0.12 | Destabilizing | 0.784 | D | 0.369 | neutral | N | 0.520604866 | None | None | N |
| T/Q | 0.1688 | likely_benign | 0.1881 | benign | -0.743 | Destabilizing | 0.704 | D | 0.299 | neutral | None | None | None | None | N |
| T/R | 0.1085 | likely_benign | 0.1184 | benign | -0.435 | Destabilizing | 0.543 | D | 0.281 | neutral | None | None | None | None | N |
| T/S | 0.1307 | likely_benign | 0.1361 | benign | -0.765 | Destabilizing | 0.01 | N | 0.094 | neutral | N | 0.473586175 | None | None | N |
| T/V | 0.1326 | likely_benign | 0.1416 | benign | -0.12 | Destabilizing | 0.828 | D | 0.175 | neutral | None | None | None | None | N |
| T/W | 0.6399 | likely_pathogenic | 0.6415 | pathogenic | -0.56 | Destabilizing | 0.995 | D | 0.304 | neutral | None | None | None | None | N |
| T/Y | 0.2777 | likely_benign | 0.2893 | benign | -0.336 | Destabilizing | 0.981 | D | 0.313 | 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.