Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32335 | 97228;97229;97230 | chr2:178542851;178542850;178542849 | chr2:179407578;179407577;179407576 |
| N2AB | 30694 | 92305;92306;92307 | chr2:178542851;178542850;178542849 | chr2:179407578;179407577;179407576 |
| N2A | 29767 | 89524;89525;89526 | chr2:178542851;178542850;178542849 | chr2:179407578;179407577;179407576 |
| N2B | 23270 | 70033;70034;70035 | chr2:178542851;178542850;178542849 | chr2:179407578;179407577;179407576 |
| Novex-1 | 23395 | 70408;70409;70410 | chr2:178542851;178542850;178542849 | chr2:179407578;179407577;179407576 |
| Novex-2 | 23462 | 70609;70610;70611 | chr2:178542851;178542850;178542849 | chr2:179407578;179407577;179407576 |
| 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/L | rs771804243  |
None | 0.035 | N | 0.291 | 0.245 | 0.496495002422 | gnomAD-4.0.0 | 1.3684E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79892E-06 | 0 | 0 |
| P/R | rs771804243 |
0.174 | 0.976 | N | 0.455 | 0.34 | 0.455722563999 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| P/R | rs771804243 |
0.174 | 0.976 | N | 0.455 | 0.34 | 0.455722563999 | gnomAD-4.0.0 | 4.1052E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39676E-06 | 0 | 0 |
| P/S | rs779886174 |
-0.228 | 0.852 | N | 0.339 | 0.263 | 0.375147631797 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 4.64E-05 | 0 | 0 |
| P/S | rs779886174 |
-0.228 | 0.852 | N | 0.339 | 0.263 | 0.375147631797 | gnomAD-4.0.0 | 3.18243E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77285E-05 | None | 1.88274E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0698 | likely_benign | 0.0626 | benign | -0.757 | Destabilizing | 0.134 | N | 0.181 | neutral | N | 0.429873674 | None | None | N |
| P/C | 0.4979 | ambiguous | 0.394 | ambiguous | -0.569 | Destabilizing | 0.999 | D | 0.497 | neutral | None | None | None | None | N |
| P/D | 0.552 | ambiguous | 0.4729 | ambiguous | -0.534 | Destabilizing | 0.939 | D | 0.399 | neutral | None | None | None | None | N |
| P/E | 0.2921 | likely_benign | 0.2537 | benign | -0.643 | Destabilizing | 0.884 | D | 0.341 | neutral | None | None | None | None | N |
| P/F | 0.3847 | ambiguous | 0.3119 | benign | -0.919 | Destabilizing | 0.982 | D | 0.503 | neutral | None | None | None | None | N |
| P/G | 0.3548 | ambiguous | 0.292 | benign | -0.922 | Destabilizing | 0.884 | D | 0.443 | neutral | None | None | None | None | N |
| P/H | 0.2094 | likely_benign | 0.1668 | benign | -0.553 | Destabilizing | 0.997 | D | 0.481 | neutral | N | 0.494037349 | None | None | N |
| P/I | 0.1897 | likely_benign | 0.1558 | benign | -0.46 | Destabilizing | 0.884 | D | 0.457 | neutral | None | None | None | None | N |
| P/K | 0.2625 | likely_benign | 0.2214 | benign | -0.655 | Destabilizing | 0.884 | D | 0.355 | neutral | None | None | None | None | N |
| P/L | 0.0874 | likely_benign | 0.0739 | benign | -0.46 | Destabilizing | 0.035 | N | 0.291 | neutral | N | 0.456425557 | None | None | N |
| P/M | 0.2176 | likely_benign | 0.182 | benign | -0.368 | Destabilizing | 0.982 | D | 0.495 | neutral | None | None | None | None | N |
| P/N | 0.3642 | ambiguous | 0.2987 | benign | -0.281 | Destabilizing | 0.991 | D | 0.467 | neutral | None | None | None | None | N |
| P/Q | 0.1356 | likely_benign | 0.1194 | benign | -0.553 | Destabilizing | 0.373 | N | 0.194 | neutral | None | None | None | None | N |
| P/R | 0.1866 | likely_benign | 0.1564 | benign | -0.109 | Destabilizing | 0.976 | D | 0.455 | neutral | N | 0.473664524 | None | None | N |
| P/S | 0.1218 | likely_benign | 0.1008 | benign | -0.647 | Destabilizing | 0.852 | D | 0.339 | neutral | N | 0.48472688 | None | None | N |
| P/T | 0.1071 | likely_benign | 0.089 | benign | -0.66 | Destabilizing | 0.92 | D | 0.347 | neutral | N | 0.454403973 | None | None | N |
| P/V | 0.1269 | likely_benign | 0.1073 | benign | -0.524 | Destabilizing | 0.884 | D | 0.433 | neutral | None | None | None | None | N |
| P/W | 0.6385 | likely_pathogenic | 0.5406 | ambiguous | -0.998 | Destabilizing | 0.999 | D | 0.544 | neutral | None | None | None | None | N |
| P/Y | 0.3901 | ambiguous | 0.3287 | benign | -0.714 | Destabilizing | 0.997 | D | 0.503 | 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.