Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35358 | 106297;106298;106299 | chr2:178530543;178530542;178530541 | chr2:179395270;179395269;179395268 |
| N2AB | 33717 | 101374;101375;101376 | chr2:178530543;178530542;178530541 | chr2:179395270;179395269;179395268 |
| N2A | 32790 | 98593;98594;98595 | chr2:178530543;178530542;178530541 | chr2:179395270;179395269;179395268 |
| N2B | 26293 | 79102;79103;79104 | chr2:178530543;178530542;178530541 | chr2:179395270;179395269;179395268 |
| Novex-1 | 26418 | 79477;79478;79479 | chr2:178530543;178530542;178530541 | chr2:179395270;179395269;179395268 |
| Novex-2 | 26485 | 79678;79679;79680 | chr2:178530543;178530542;178530541 | chr2:179395270;179395269;179395268 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/D | rs1172243981  |
None | 0.055 | N | 0.689 | 0.224 | 0.563099480232 | gnomAD-4.0.0 | 6.84142E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99395E-07 | 0 | 0 |
| V/G | rs1172243981 |
-2.985 | 0.055 | N | 0.686 | 0.184 | 0.549755530797 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.56E-05 | None | 0 | None | 0 | 0 | 0 |
| V/G | rs1172243981 |
-2.985 | 0.055 | N | 0.686 | 0.184 | 0.549755530797 | gnomAD-4.0.0 | 6.84142E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.51902E-05 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1822 | likely_benign | 0.1735 | benign | -2.106 | Highly Destabilizing | 0.005 | N | 0.385 | neutral | N | 0.481517058 | None | None | N |
| V/C | 0.6468 | likely_pathogenic | 0.649 | pathogenic | -1.589 | Destabilizing | 0.628 | D | 0.677 | prob.neutral | None | None | None | None | N |
| V/D | 0.4144 | ambiguous | 0.3955 | ambiguous | -2.792 | Highly Destabilizing | 0.055 | N | 0.689 | prob.neutral | N | 0.465361401 | None | None | N |
| V/E | 0.3188 | likely_benign | 0.3084 | benign | -2.574 | Highly Destabilizing | 0.072 | N | 0.687 | prob.neutral | None | None | None | None | N |
| V/F | 0.1616 | likely_benign | 0.1613 | benign | -1.174 | Destabilizing | 0.171 | N | 0.727 | prob.delet. | N | 0.438356376 | None | None | N |
| V/G | 0.286 | likely_benign | 0.2728 | benign | -2.624 | Highly Destabilizing | 0.055 | N | 0.686 | prob.neutral | N | 0.447510635 | None | None | N |
| V/H | 0.4992 | ambiguous | 0.4945 | ambiguous | -2.398 | Highly Destabilizing | 0.628 | D | 0.685 | prob.neutral | None | None | None | None | N |
| V/I | 0.0686 | likely_benign | 0.0685 | benign | -0.652 | Destabilizing | None | N | 0.233 | neutral | N | 0.4859228 | None | None | N |
| V/K | 0.3816 | ambiguous | 0.3704 | ambiguous | -1.64 | Destabilizing | 0.072 | N | 0.688 | prob.neutral | None | None | None | None | N |
| V/L | 0.1818 | likely_benign | 0.1751 | benign | -0.652 | Destabilizing | 0.002 | N | 0.397 | neutral | N | 0.472550858 | None | None | N |
| V/M | 0.1383 | likely_benign | 0.1295 | benign | -0.763 | Destabilizing | 0.007 | N | 0.391 | neutral | None | None | None | None | N |
| V/N | 0.2532 | likely_benign | 0.2428 | benign | -1.97 | Destabilizing | 0.072 | N | 0.705 | prob.neutral | None | None | None | None | N |
| V/P | 0.9682 | likely_pathogenic | 0.966 | pathogenic | -1.112 | Destabilizing | 0.136 | N | 0.718 | prob.delet. | None | None | None | None | N |
| V/Q | 0.3237 | likely_benign | 0.3165 | benign | -1.805 | Destabilizing | 0.356 | N | 0.705 | prob.neutral | None | None | None | None | N |
| V/R | 0.2752 | likely_benign | 0.2747 | benign | -1.501 | Destabilizing | 0.214 | N | 0.716 | prob.delet. | None | None | None | None | N |
| V/S | 0.1793 | likely_benign | 0.1701 | benign | -2.544 | Highly Destabilizing | 0.003 | N | 0.544 | neutral | None | None | None | None | N |
| V/T | 0.1314 | likely_benign | 0.1288 | benign | -2.196 | Highly Destabilizing | None | N | 0.236 | neutral | None | None | None | None | N |
| V/W | 0.7913 | likely_pathogenic | 0.7883 | pathogenic | -1.729 | Destabilizing | 0.864 | D | 0.707 | prob.neutral | None | None | None | None | N |
| V/Y | 0.5071 | ambiguous | 0.5062 | ambiguous | -1.38 | Destabilizing | 0.356 | N | 0.697 | prob.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.