Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27162 | 81709;81710;81711 | chr2:178564648;178564647;178564646 | chr2:179429375;179429374;179429373 |
| N2AB | 25521 | 76786;76787;76788 | chr2:178564648;178564647;178564646 | chr2:179429375;179429374;179429373 |
| N2A | 24594 | 74005;74006;74007 | chr2:178564648;178564647;178564646 | chr2:179429375;179429374;179429373 |
| N2B | 18097 | 54514;54515;54516 | chr2:178564648;178564647;178564646 | chr2:179429375;179429374;179429373 |
| Novex-1 | 18222 | 54889;54890;54891 | chr2:178564648;178564647;178564646 | chr2:179429375;179429374;179429373 |
| Novex-2 | 18289 | 55090;55091;55092 | chr2:178564648;178564647;178564646 | chr2:179429375;179429374;179429373 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/L | rs763903239  |
0.232 | 0.666 | N | 0.607 | 0.335 | 0.447213685739 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | I | None | 1.6533E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/L | rs763903239 |
0.232 | 0.666 | N | 0.607 | 0.335 | 0.447213685739 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/L | rs763903239 |
0.232 | 0.666 | N | 0.607 | 0.335 | 0.447213685739 | gnomAD-4.0.0 | 7.43772E-06 | None | None | None | None | I | None | 1.60226E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/P | rs1387276571 |
0.196 | 0.989 | D | 0.637 | 0.425 | 0.250039746154 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.61E-05 | None | 0 | None | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.3618 | ambiguous | 0.2979 | benign | -0.659 | Destabilizing | 0.451 | N | 0.577 | neutral | N | 0.510825616 | None | None | I |
| S/C | 0.28 | likely_benign | 0.2333 | benign | -0.402 | Destabilizing | 0.037 | N | 0.573 | neutral | None | None | None | None | I |
| S/D | 0.9904 | likely_pathogenic | 0.9889 | pathogenic | -0.689 | Destabilizing | 0.991 | D | 0.543 | neutral | None | None | None | None | I |
| S/E | 0.9951 | likely_pathogenic | 0.9944 | pathogenic | -0.555 | Destabilizing | 0.991 | D | 0.546 | neutral | None | None | None | None | I |
| S/F | 0.9858 | likely_pathogenic | 0.9795 | pathogenic | -0.468 | Destabilizing | 0.037 | N | 0.511 | neutral | None | None | None | None | I |
| S/G | 0.4267 | ambiguous | 0.3799 | ambiguous | -1.029 | Destabilizing | 0.915 | D | 0.593 | neutral | None | None | None | None | I |
| S/H | 0.9882 | likely_pathogenic | 0.9869 | pathogenic | -1.339 | Destabilizing | 0.998 | D | 0.615 | neutral | None | None | None | None | I |
| S/I | 0.9509 | likely_pathogenic | 0.9361 | pathogenic | 0.26 | Stabilizing | 0.903 | D | 0.621 | neutral | None | None | None | None | I |
| S/K | 0.9991 | likely_pathogenic | 0.999 | pathogenic | -0.311 | Destabilizing | 0.991 | D | 0.559 | neutral | None | None | None | None | I |
| S/L | 0.7998 | likely_pathogenic | 0.749 | pathogenic | 0.26 | Stabilizing | 0.666 | D | 0.607 | neutral | N | 0.50230324 | None | None | I |
| S/M | 0.8659 | likely_pathogenic | 0.8416 | pathogenic | 0.179 | Stabilizing | 0.993 | D | 0.615 | neutral | None | None | None | None | I |
| S/N | 0.9368 | likely_pathogenic | 0.9267 | pathogenic | -0.708 | Destabilizing | 0.991 | D | 0.576 | neutral | None | None | None | None | I |
| S/P | 0.9846 | likely_pathogenic | 0.9784 | pathogenic | -0.01 | Destabilizing | 0.989 | D | 0.637 | neutral | D | 0.524120933 | None | None | I |
| S/Q | 0.991 | likely_pathogenic | 0.9904 | pathogenic | -0.582 | Destabilizing | 0.991 | D | 0.567 | neutral | None | None | None | None | I |
| S/R | 0.998 | likely_pathogenic | 0.9976 | pathogenic | -0.52 | Destabilizing | 0.991 | D | 0.636 | neutral | None | None | None | None | I |
| S/T | 0.2149 | likely_benign | 0.2059 | benign | -0.522 | Destabilizing | 0.799 | D | 0.607 | neutral | N | 0.461766317 | None | None | I |
| S/V | 0.8788 | likely_pathogenic | 0.8477 | pathogenic | -0.01 | Destabilizing | 0.841 | D | 0.617 | neutral | None | None | None | None | I |
| S/W | 0.99 | likely_pathogenic | 0.9872 | pathogenic | -0.623 | Destabilizing | 0.998 | D | 0.799 | deleterious | None | None | None | None | I |
| S/Y | 0.9854 | likely_pathogenic | 0.9808 | pathogenic | -0.223 | Destabilizing | 0.903 | D | 0.763 | deleterious | 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.