Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26136 | 78631;78632;78633 | chr2:178567726;178567725;178567724 | chr2:179432453;179432452;179432451 |
| N2AB | 24495 | 73708;73709;73710 | chr2:178567726;178567725;178567724 | chr2:179432453;179432452;179432451 |
| N2A | 23568 | 70927;70928;70929 | chr2:178567726;178567725;178567724 | chr2:179432453;179432452;179432451 |
| N2B | 17071 | 51436;51437;51438 | chr2:178567726;178567725;178567724 | chr2:179432453;179432452;179432451 |
| Novex-1 | 17196 | 51811;51812;51813 | chr2:178567726;178567725;178567724 | chr2:179432453;179432452;179432451 |
| Novex-2 | 17263 | 52012;52013;52014 | chr2:178567726;178567725;178567724 | chr2:179432453;179432452;179432451 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | None | None | 0.007 | N | 0.148 | 0.168 | 0.506432333661 | gnomAD-4.0.0 | 1.59486E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02994E-05 |
| M/T | rs1454726736  |
0.042 | 0.684 | N | 0.321 | 0.4 | 0.659672427465 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| M/T | rs1454726736 |
0.042 | 0.684 | N | 0.321 | 0.4 | 0.659672427465 | gnomAD-4.0.0 | 6.37853E-06 | None | None | None | None | N | None | 1.13289E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 5.73339E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.8507 | likely_pathogenic | 0.8669 | pathogenic | -1.79 | Destabilizing | 0.543 | D | 0.364 | neutral | None | None | None | None | N |
| M/C | 0.9091 | likely_pathogenic | 0.9017 | pathogenic | -1.245 | Destabilizing | 0.996 | D | 0.41 | neutral | None | None | None | None | N |
| M/D | 0.9852 | likely_pathogenic | 0.987 | pathogenic | -0.591 | Destabilizing | 0.984 | D | 0.451 | neutral | None | None | None | None | N |
| M/E | 0.8852 | likely_pathogenic | 0.8947 | pathogenic | -0.557 | Destabilizing | 0.984 | D | 0.406 | neutral | None | None | None | None | N |
| M/F | 0.6993 | likely_pathogenic | 0.7029 | pathogenic | -0.709 | Destabilizing | 0.742 | D | 0.376 | neutral | None | None | None | None | N |
| M/G | 0.9148 | likely_pathogenic | 0.922 | pathogenic | -2.109 | Highly Destabilizing | 0.953 | D | 0.399 | neutral | None | None | None | None | N |
| M/H | 0.8767 | likely_pathogenic | 0.8821 | pathogenic | -1.118 | Destabilizing | 0.996 | D | 0.445 | neutral | None | None | None | None | N |
| M/I | 0.6895 | likely_pathogenic | 0.6953 | pathogenic | -0.963 | Destabilizing | 0.007 | N | 0.148 | neutral | N | 0.483019434 | None | None | N |
| M/K | 0.624 | likely_pathogenic | 0.6525 | pathogenic | -0.667 | Destabilizing | 0.815 | D | 0.354 | neutral | N | 0.487115745 | None | None | N |
| M/L | 0.2015 | likely_benign | 0.2135 | benign | -0.963 | Destabilizing | 0.028 | N | 0.212 | neutral | N | 0.440114019 | None | None | N |
| M/N | 0.8242 | likely_pathogenic | 0.8357 | pathogenic | -0.51 | Destabilizing | 0.984 | D | 0.443 | neutral | None | None | None | None | N |
| M/P | 0.9942 | likely_pathogenic | 0.9935 | pathogenic | -1.213 | Destabilizing | 0.984 | D | 0.441 | neutral | None | None | None | None | N |
| M/Q | 0.4964 | ambiguous | 0.528 | ambiguous | -0.59 | Destabilizing | 0.984 | D | 0.425 | neutral | None | None | None | None | N |
| M/R | 0.6514 | likely_pathogenic | 0.6765 | pathogenic | -0.156 | Destabilizing | 0.979 | D | 0.411 | neutral | N | 0.486982459 | None | None | N |
| M/S | 0.8122 | likely_pathogenic | 0.8289 | pathogenic | -1.133 | Destabilizing | 0.854 | D | 0.339 | neutral | None | None | None | None | N |
| M/T | 0.6158 | likely_pathogenic | 0.642 | pathogenic | -0.991 | Destabilizing | 0.684 | D | 0.321 | neutral | N | 0.475496029 | None | None | N |
| M/V | 0.2303 | likely_benign | 0.2407 | benign | -1.213 | Destabilizing | 0.063 | N | 0.243 | neutral | N | 0.436900355 | None | None | N |
| M/W | 0.9286 | likely_pathogenic | 0.9208 | pathogenic | -0.635 | Destabilizing | 0.996 | D | 0.435 | neutral | None | None | None | None | N |
| M/Y | 0.8806 | likely_pathogenic | 0.8744 | pathogenic | -0.689 | Destabilizing | 0.953 | D | 0.418 | 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.