Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21238 | 63937;63938;63939 | chr2:178587597;178587596;178587595 | chr2:179452324;179452323;179452322 |
| N2AB | 19597 | 59014;59015;59016 | chr2:178587597;178587596;178587595 | chr2:179452324;179452323;179452322 |
| N2A | 18670 | 56233;56234;56235 | chr2:178587597;178587596;178587595 | chr2:179452324;179452323;179452322 |
| N2B | 12173 | 36742;36743;36744 | chr2:178587597;178587596;178587595 | chr2:179452324;179452323;179452322 |
| Novex-1 | 12298 | 37117;37118;37119 | chr2:178587597;178587596;178587595 | chr2:179452324;179452323;179452322 |
| Novex-2 | 12365 | 37318;37319;37320 | chr2:178587597;178587596;178587595 | chr2:179452324;179452323;179452322 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs190432620  |
-0.03 | 1.0 | D | 0.731 | 0.384 | None | gnomAD-2.1.1 | 2.02E-05 | None | None | None | None | I | None | 6.48E-05 | 0 | None | 0 | 0 | None | 6.55E-05 | None | 0 | 8.93E-06 | 1.67168E-04 |
| R/C | rs190432620 |
-0.03 | 1.0 | D | 0.731 | 0.384 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| R/C | rs190432620 |
-0.03 | 1.0 | D | 0.731 | 0.384 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| R/C | rs190432620 |
-0.03 | 1.0 | D | 0.731 | 0.384 | None | gnomAD-4.0.0 | 1.11632E-05 | None | None | None | None | I | None | 1.33461E-05 | 0 | None | 0 | 2.24376E-05 | None | 0 | 0 | 1.01755E-05 | 4.39454E-05 | 0 |
| R/H | rs544396866 |
-0.612 | 1.0 | N | 0.757 | 0.409 | 0.398581233421 | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.3101E-04 | None | 0 | 0 | 1.41363E-04 |
| R/H | rs544396866 |
-0.612 | 1.0 | N | 0.757 | 0.409 | 0.398581233421 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 6.20861E-04 | 0 |
| R/H | rs544396866 |
-0.612 | 1.0 | N | 0.757 | 0.409 | 0.398581233421 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| R/H | rs544396866 |
-0.612 | 1.0 | N | 0.757 | 0.409 | 0.398581233421 | gnomAD-4.0.0 | 1.17827E-05 | None | None | None | None | I | None | 1.33415E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.08767E-06 | 1.31842E-04 | 0 |
| R/L | rs544396866 |
0.466 | 1.0 | N | 0.605 | 0.433 | 0.283761946502 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| R/L | rs544396866 |
0.466 | 1.0 | N | 0.605 | 0.433 | 0.283761946502 | gnomAD-4.0.0 | 6.84728E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16023E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9705 | likely_pathogenic | 0.9717 | pathogenic | -0.042 | Destabilizing | 0.999 | D | 0.63 | neutral | None | None | None | None | I |
| R/C | 0.7639 | likely_pathogenic | 0.7798 | pathogenic | -0.131 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | D | 0.524212021 | None | None | I |
| R/D | 0.9962 | likely_pathogenic | 0.9965 | pathogenic | -0.171 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | I |
| R/E | 0.9593 | likely_pathogenic | 0.9608 | pathogenic | -0.117 | Destabilizing | 0.999 | D | 0.675 | neutral | None | None | None | None | I |
| R/F | 0.9867 | likely_pathogenic | 0.9868 | pathogenic | -0.28 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | I |
| R/G | 0.9664 | likely_pathogenic | 0.9689 | pathogenic | -0.226 | Destabilizing | 1.0 | D | 0.605 | neutral | N | 0.497206996 | None | None | I |
| R/H | 0.5617 | ambiguous | 0.6035 | pathogenic | -0.701 | Destabilizing | 1.0 | D | 0.757 | deleterious | N | 0.489471542 | None | None | I |
| R/I | 0.9376 | likely_pathogenic | 0.9294 | pathogenic | 0.404 | Stabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| R/K | 0.4286 | ambiguous | 0.4457 | ambiguous | -0.119 | Destabilizing | 0.998 | D | 0.56 | neutral | None | None | None | None | I |
| R/L | 0.9092 | likely_pathogenic | 0.9029 | pathogenic | 0.404 | Stabilizing | 1.0 | D | 0.605 | neutral | N | 0.460981579 | None | None | I |
| R/M | 0.9534 | likely_pathogenic | 0.9503 | pathogenic | 0.048 | Stabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | I |
| R/N | 0.9903 | likely_pathogenic | 0.991 | pathogenic | 0.146 | Stabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | None | I |
| R/P | 0.973 | likely_pathogenic | 0.9717 | pathogenic | 0.275 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | N | 0.452778825 | None | None | I |
| R/Q | 0.5581 | ambiguous | 0.5829 | pathogenic | 0.022 | Stabilizing | 1.0 | D | 0.708 | prob.delet. | None | None | None | None | I |
| R/S | 0.988 | likely_pathogenic | 0.9885 | pathogenic | -0.187 | Destabilizing | 1.0 | D | 0.662 | neutral | N | 0.472404017 | None | None | I |
| R/T | 0.9707 | likely_pathogenic | 0.969 | pathogenic | -0.009 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | I |
| R/V | 0.9478 | likely_pathogenic | 0.9457 | pathogenic | 0.275 | Stabilizing | 1.0 | D | 0.7 | prob.neutral | None | None | None | None | I |
| R/W | 0.8016 | likely_pathogenic | 0.7969 | pathogenic | -0.34 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | I |
| R/Y | 0.9559 | likely_pathogenic | 0.9591 | pathogenic | 0.06 | Stabilizing | 1.0 | D | 0.708 | prob.delet. | 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.