Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18797 | 56614;56615;56616 | chr2:178599404;178599403;178599402 | chr2:179464131;179464130;179464129 |
| N2AB | 17156 | 51691;51692;51693 | chr2:178599404;178599403;178599402 | chr2:179464131;179464130;179464129 |
| N2A | 16229 | 48910;48911;48912 | chr2:178599404;178599403;178599402 | chr2:179464131;179464130;179464129 |
| N2B | 9732 | 29419;29420;29421 | chr2:178599404;178599403;178599402 | chr2:179464131;179464130;179464129 |
| Novex-1 | 9857 | 29794;29795;29796 | chr2:178599404;178599403;178599402 | chr2:179464131;179464130;179464129 |
| Novex-2 | 9924 | 29995;29996;29997 | chr2:178599404;178599403;178599402 | chr2:179464131;179464130;179464129 |
| 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/I | rs778722684  |
-0.658 | None | N | 0.177 | 0.074 | 0.112648838833 | gnomAD-2.1.1 | 1.44E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.07E-05 | 0 |
| V/I | rs778722684 |
-0.658 | None | N | 0.177 | 0.074 | 0.112648838833 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/I | rs778722684 |
-0.658 | None | N | 0.177 | 0.074 | 0.112648838833 | gnomAD-4.0.0 | 1.09231E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.01584E-05 | 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 | 0.4065 | ambiguous | 0.4461 | ambiguous | -1.12 | Destabilizing | 0.104 | N | 0.5 | neutral | D | 0.523004761 | None | None | N |
| V/C | 0.7162 | likely_pathogenic | 0.7251 | pathogenic | -1.085 | Destabilizing | 0.968 | D | 0.556 | neutral | None | None | None | None | N |
| V/D | 0.817 | likely_pathogenic | 0.8462 | pathogenic | -0.618 | Destabilizing | 0.667 | D | 0.682 | prob.neutral | D | 0.52637002 | None | None | N |
| V/E | 0.6791 | likely_pathogenic | 0.7222 | pathogenic | -0.666 | Destabilizing | 0.726 | D | 0.597 | neutral | None | None | None | None | N |
| V/F | 0.25 | likely_benign | 0.2955 | benign | -1.158 | Destabilizing | 0.497 | N | 0.549 | neutral | N | 0.489783117 | None | None | N |
| V/G | 0.5564 | ambiguous | 0.5849 | pathogenic | -1.352 | Destabilizing | 0.667 | D | 0.641 | neutral | N | 0.509444308 | None | None | N |
| V/H | 0.778 | likely_pathogenic | 0.8123 | pathogenic | -0.941 | Destabilizing | 0.968 | D | 0.686 | prob.neutral | None | None | None | None | N |
| V/I | 0.0577 | likely_benign | 0.0623 | benign | -0.615 | Destabilizing | None | N | 0.177 | neutral | N | 0.458894567 | None | None | N |
| V/K | 0.54 | ambiguous | 0.5861 | pathogenic | -0.722 | Destabilizing | 0.726 | D | 0.607 | neutral | None | None | None | None | N |
| V/L | 0.171 | likely_benign | 0.2128 | benign | -0.615 | Destabilizing | 0.009 | N | 0.318 | neutral | D | 0.522311328 | None | None | N |
| V/M | 0.1894 | likely_benign | 0.2033 | benign | -0.563 | Destabilizing | 0.567 | D | 0.503 | neutral | None | None | None | None | N |
| V/N | 0.5719 | likely_pathogenic | 0.6101 | pathogenic | -0.508 | Destabilizing | 0.89 | D | 0.693 | prob.neutral | None | None | None | None | N |
| V/P | 0.8129 | likely_pathogenic | 0.8662 | pathogenic | -0.749 | Destabilizing | 0.89 | D | 0.615 | neutral | None | None | None | None | N |
| V/Q | 0.5732 | likely_pathogenic | 0.6168 | pathogenic | -0.738 | Destabilizing | 0.89 | D | 0.623 | neutral | None | None | None | None | N |
| V/R | 0.4438 | ambiguous | 0.517 | ambiguous | -0.298 | Destabilizing | 0.726 | D | 0.689 | prob.neutral | None | None | None | None | N |
| V/S | 0.5099 | ambiguous | 0.5416 | ambiguous | -1.059 | Destabilizing | 0.726 | D | 0.518 | neutral | None | None | None | None | N |
| V/T | 0.3816 | ambiguous | 0.4006 | ambiguous | -0.996 | Destabilizing | 0.272 | N | 0.486 | neutral | None | None | None | None | N |
| V/W | 0.8805 | likely_pathogenic | 0.9058 | pathogenic | -1.229 | Destabilizing | 0.968 | D | 0.686 | prob.neutral | None | None | None | None | N |
| V/Y | 0.6536 | likely_pathogenic | 0.704 | pathogenic | -0.901 | Destabilizing | 0.726 | D | 0.578 | 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.