Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34138 | 102637;102638;102639 | chr2:178534203;178534202;178534201 | chr2:179398930;179398929;179398928 |
| N2AB | 32497 | 97714;97715;97716 | chr2:178534203;178534202;178534201 | chr2:179398930;179398929;179398928 |
| N2A | 31570 | 94933;94934;94935 | chr2:178534203;178534202;178534201 | chr2:179398930;179398929;179398928 |
| N2B | 25073 | 75442;75443;75444 | chr2:178534203;178534202;178534201 | chr2:179398930;179398929;179398928 |
| Novex-1 | 25198 | 75817;75818;75819 | chr2:178534203;178534202;178534201 | chr2:179398930;179398929;179398928 |
| Novex-2 | 25265 | 76018;76019;76020 | chr2:178534203;178534202;178534201 | chr2:179398930;179398929;179398928 |
| 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/A | rs761112704  |
-0.77 | 0.165 | N | 0.515 | 0.142 | 0.542764462858 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| V/A | rs761112704 |
-0.77 | 0.165 | N | 0.515 | 0.142 | 0.542764462858 | gnomAD-4.0.0 | 1.3683E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99408E-07 | 0 | 1.65634E-05 |
| V/D | None | None | 0.773 | N | 0.63 | 0.321 | 0.755519617258 | gnomAD-4.0.0 | 6.84151E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99408E-07 | 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 | 0.4534 | ambiguous | 0.3465 | ambiguous | -0.824 | Destabilizing | 0.165 | N | 0.515 | neutral | N | 0.474024309 | None | None | I |
| V/C | 0.8814 | likely_pathogenic | 0.8193 | pathogenic | -0.743 | Destabilizing | 0.981 | D | 0.559 | neutral | None | None | None | None | I |
| V/D | 0.8072 | likely_pathogenic | 0.648 | pathogenic | -0.305 | Destabilizing | 0.773 | D | 0.63 | neutral | N | 0.475237818 | None | None | I |
| V/E | 0.6896 | likely_pathogenic | 0.4731 | ambiguous | -0.391 | Destabilizing | 0.388 | N | 0.604 | neutral | None | None | None | None | I |
| V/F | 0.3563 | ambiguous | 0.2821 | benign | -0.882 | Destabilizing | 0.627 | D | 0.585 | neutral | N | 0.456998774 | None | None | I |
| V/G | 0.6262 | likely_pathogenic | 0.501 | ambiguous | -1.019 | Destabilizing | 0.492 | N | 0.608 | neutral | N | 0.475411176 | None | None | I |
| V/H | 0.8732 | likely_pathogenic | 0.7059 | pathogenic | -0.526 | Destabilizing | 0.981 | D | 0.617 | neutral | None | None | None | None | I |
| V/I | 0.0835 | likely_benign | 0.0829 | benign | -0.444 | Destabilizing | 0.001 | N | 0.238 | neutral | N | 0.474544384 | None | None | I |
| V/K | 0.6905 | likely_pathogenic | 0.3952 | ambiguous | -0.583 | Destabilizing | 0.241 | N | 0.538 | neutral | None | None | None | None | I |
| V/L | 0.2726 | likely_benign | 0.2181 | benign | -0.444 | Destabilizing | 0.033 | N | 0.402 | neutral | N | 0.474024309 | None | None | I |
| V/M | 0.2928 | likely_benign | 0.2335 | benign | -0.377 | Destabilizing | 0.69 | D | 0.546 | neutral | None | None | None | None | I |
| V/N | 0.643 | likely_pathogenic | 0.4457 | ambiguous | -0.303 | Destabilizing | 0.818 | D | 0.631 | neutral | None | None | None | None | I |
| V/P | 0.8882 | likely_pathogenic | 0.8312 | pathogenic | -0.534 | Destabilizing | 0.932 | D | 0.633 | neutral | None | None | None | None | I |
| V/Q | 0.6887 | likely_pathogenic | 0.4294 | ambiguous | -0.545 | Destabilizing | 0.69 | D | 0.629 | neutral | None | None | None | None | I |
| V/R | 0.6073 | likely_pathogenic | 0.342 | ambiguous | -0.061 | Destabilizing | 0.002 | N | 0.443 | neutral | None | None | None | None | I |
| V/S | 0.577 | likely_pathogenic | 0.4055 | ambiguous | -0.784 | Destabilizing | 0.563 | D | 0.596 | neutral | None | None | None | None | I |
| V/T | 0.4586 | ambiguous | 0.3224 | benign | -0.761 | Destabilizing | 0.388 | N | 0.482 | neutral | None | None | None | None | I |
| V/W | 0.9585 | likely_pathogenic | 0.9218 | pathogenic | -0.943 | Destabilizing | 0.981 | D | 0.663 | neutral | None | None | None | None | I |
| V/Y | 0.8104 | likely_pathogenic | 0.6708 | pathogenic | -0.647 | Destabilizing | 0.818 | D | 0.585 | 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.