Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17282 | 52069;52070;52071 | chr2:178609466;178609465;178609464 | chr2:179474193;179474192;179474191 |
| N2AB | 15641 | 47146;47147;47148 | chr2:178609466;178609465;178609464 | chr2:179474193;179474192;179474191 |
| N2A | 14714 | 44365;44366;44367 | chr2:178609466;178609465;178609464 | chr2:179474193;179474192;179474191 |
| N2B | 8217 | 24874;24875;24876 | chr2:178609466;178609465;178609464 | chr2:179474193;179474192;179474191 |
| Novex-1 | 8342 | 25249;25250;25251 | chr2:178609466;178609465;178609464 | chr2:179474193;179474192;179474191 |
| Novex-2 | 8409 | 25450;25451;25452 | chr2:178609466;178609465;178609464 | chr2:179474193;179474192;179474191 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs1490005480  |
-1.644 | 0.012 | N | 0.708 | 0.08 | 0.342400092842 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14758E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1490005480 |
-1.644 | 0.012 | N | 0.708 | 0.08 | 0.342400092842 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1490005480 |
-1.644 | 0.012 | N | 0.708 | 0.08 | 0.342400092842 | gnomAD-4.0.0 | 1.31733E-05 | None | None | None | None | N | None | 4.83395E-05 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3962 | ambiguous | 0.4105 | ambiguous | -2.566 | Highly Destabilizing | 0.007 | N | 0.617 | neutral | None | None | None | None | N |
| I/C | 0.4645 | ambiguous | 0.474 | ambiguous | -1.764 | Destabilizing | 0.628 | D | 0.775 | deleterious | None | None | None | None | N |
| I/D | 0.7598 | likely_pathogenic | 0.7541 | pathogenic | -2.949 | Highly Destabilizing | 0.072 | N | 0.773 | deleterious | None | None | None | None | N |
| I/E | 0.4197 | ambiguous | 0.4035 | ambiguous | -2.77 | Highly Destabilizing | 0.072 | N | 0.772 | deleterious | None | None | None | None | N |
| I/F | 0.0992 | likely_benign | 0.1008 | benign | -1.551 | Destabilizing | 0.016 | N | 0.592 | neutral | None | None | None | None | N |
| I/G | 0.6241 | likely_pathogenic | 0.6283 | pathogenic | -3.055 | Highly Destabilizing | 0.072 | N | 0.734 | prob.delet. | None | None | None | None | N |
| I/H | 0.3419 | ambiguous | 0.3295 | benign | -2.49 | Highly Destabilizing | 0.214 | N | 0.822 | deleterious | None | None | None | None | N |
| I/K | 0.2901 | likely_benign | 0.2754 | benign | -1.988 | Destabilizing | 0.055 | N | 0.754 | deleterious | N | 0.391407634 | None | None | N |
| I/L | 0.065 | likely_benign | 0.0674 | benign | -1.166 | Destabilizing | None | N | 0.134 | neutral | N | 0.327913516 | None | None | N |
| I/M | 0.0624 | likely_benign | 0.0666 | benign | -1.058 | Destabilizing | None | N | 0.261 | neutral | N | 0.381249355 | None | None | N |
| I/N | 0.2975 | likely_benign | 0.3027 | benign | -2.22 | Highly Destabilizing | 0.072 | N | 0.772 | deleterious | None | None | None | None | N |
| I/P | 0.9732 | likely_pathogenic | 0.972 | pathogenic | -1.613 | Destabilizing | 0.136 | N | 0.803 | deleterious | None | None | None | None | N |
| I/Q | 0.277 | likely_benign | 0.2647 | benign | -2.157 | Highly Destabilizing | 0.072 | N | 0.783 | deleterious | None | None | None | None | N |
| I/R | 0.2366 | likely_benign | 0.2274 | benign | -1.583 | Destabilizing | 0.055 | N | 0.781 | deleterious | N | 0.40612637 | None | None | N |
| I/S | 0.2884 | likely_benign | 0.307 | benign | -2.856 | Highly Destabilizing | 0.001 | N | 0.514 | neutral | None | None | None | None | N |
| I/T | 0.2204 | likely_benign | 0.2325 | benign | -2.552 | Highly Destabilizing | 0.012 | N | 0.708 | prob.delet. | N | 0.370685645 | None | None | N |
| I/V | 0.091 | likely_benign | 0.0935 | benign | -1.613 | Destabilizing | 0.002 | N | 0.311 | neutral | N | 0.440969663 | None | None | N |
| I/W | 0.4691 | ambiguous | 0.463 | ambiguous | -1.956 | Destabilizing | 0.628 | D | 0.802 | deleterious | None | None | None | None | N |
| I/Y | 0.2524 | likely_benign | 0.258 | benign | -1.698 | Destabilizing | None | N | 0.433 | 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.