Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18847 | 56764;56765;56766 | chr2:178599254;178599253;178599252 | chr2:179463981;179463980;179463979 |
| N2AB | 17206 | 51841;51842;51843 | chr2:178599254;178599253;178599252 | chr2:179463981;179463980;179463979 |
| N2A | 16279 | 49060;49061;49062 | chr2:178599254;178599253;178599252 | chr2:179463981;179463980;179463979 |
| N2B | 9782 | 29569;29570;29571 | chr2:178599254;178599253;178599252 | chr2:179463981;179463980;179463979 |
| Novex-1 | 9907 | 29944;29945;29946 | chr2:178599254;178599253;178599252 | chr2:179463981;179463980;179463979 |
| Novex-2 | 9974 | 30145;30146;30147 | chr2:178599254;178599253;178599252 | chr2:179463981;179463980;179463979 |
| 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/A | None | None | 0.91 | N | 0.509 | 0.194 | 0.32306181527 | gnomAD-4.0.0 | 1.41796E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.15245E-07 | 0 | 1.71892E-05 |
| P/H | None | None | 0.998 | N | 0.668 | 0.323 | 0.473538153929 | gnomAD-4.0.0 | 1.73601E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.71444E-05 | 0 |
| P/S | rs763491342  |
-1.449 | 0.925 | N | 0.51 | 0.223 | 0.29132392195 | gnomAD-2.1.1 | 9.82E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.26936E-04 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs763491342 |
-1.449 | 0.925 | N | 0.51 | 0.223 | 0.29132392195 | gnomAD-4.0.0 | 1.41796E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.11823E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1117 | likely_benign | 0.1184 | benign | -1.329 | Destabilizing | 0.91 | D | 0.509 | neutral | N | 0.442655679 | None | None | N |
| P/C | 0.4755 | ambiguous | 0.4993 | ambiguous | -0.856 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| P/D | 0.5 | ambiguous | 0.5597 | ambiguous | -1.264 | Destabilizing | 0.97 | D | 0.516 | neutral | None | None | None | None | N |
| P/E | 0.3278 | likely_benign | 0.3718 | ambiguous | -1.278 | Destabilizing | 0.942 | D | 0.503 | neutral | None | None | None | None | N |
| P/F | 0.5842 | likely_pathogenic | 0.6063 | pathogenic | -1.034 | Destabilizing | 0.999 | D | 0.715 | prob.delet. | None | None | None | None | N |
| P/G | 0.2467 | likely_benign | 0.271 | benign | -1.622 | Destabilizing | 0.985 | D | 0.589 | neutral | None | None | None | None | N |
| P/H | 0.2282 | likely_benign | 0.2416 | benign | -1.142 | Destabilizing | 0.998 | D | 0.668 | neutral | N | 0.445157266 | None | None | N |
| P/I | 0.4212 | ambiguous | 0.438 | ambiguous | -0.632 | Destabilizing | 0.991 | D | 0.685 | prob.neutral | None | None | None | None | N |
| P/K | 0.3576 | ambiguous | 0.3762 | ambiguous | -1.243 | Destabilizing | 0.942 | D | 0.493 | neutral | None | None | None | None | N |
| P/L | 0.1634 | likely_benign | 0.1725 | benign | -0.632 | Destabilizing | 0.961 | D | 0.614 | neutral | N | 0.43446027 | None | None | N |
| P/M | 0.3523 | ambiguous | 0.3684 | ambiguous | -0.508 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| P/N | 0.3057 | likely_benign | 0.3465 | ambiguous | -0.987 | Destabilizing | 0.996 | D | 0.615 | neutral | None | None | None | None | N |
| P/Q | 0.1767 | likely_benign | 0.1926 | benign | -1.166 | Destabilizing | 0.746 | D | 0.259 | neutral | None | None | None | None | N |
| P/R | 0.2579 | likely_benign | 0.274 | benign | -0.677 | Destabilizing | 0.989 | D | 0.618 | neutral | N | 0.404790724 | None | None | N |
| P/S | 0.1287 | likely_benign | 0.1391 | benign | -1.434 | Destabilizing | 0.925 | D | 0.51 | neutral | N | 0.392802861 | None | None | N |
| P/T | 0.1104 | likely_benign | 0.1135 | benign | -1.341 | Destabilizing | 0.122 | N | 0.235 | neutral | N | 0.339776453 | None | None | N |
| P/V | 0.2699 | likely_benign | 0.277 | benign | -0.83 | Destabilizing | 0.97 | D | 0.59 | neutral | None | None | None | None | N |
| P/W | 0.6281 | likely_pathogenic | 0.6636 | pathogenic | -1.214 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| P/Y | 0.491 | ambiguous | 0.5071 | ambiguous | -0.939 | Destabilizing | 0.999 | D | 0.721 | prob.delet. | 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.