Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2831 | 8716;8717;8718 | chr2:178770210;178770209;178770208 | chr2:179634937;179634936;179634935 |
| N2AB | 2831 | 8716;8717;8718 | chr2:178770210;178770209;178770208 | chr2:179634937;179634936;179634935 |
| N2A | 2831 | 8716;8717;8718 | chr2:178770210;178770209;178770208 | chr2:179634937;179634936;179634935 |
| N2B | 2785 | 8578;8579;8580 | chr2:178770210;178770209;178770208 | chr2:179634937;179634936;179634935 |
| Novex-1 | 2785 | 8578;8579;8580 | chr2:178770210;178770209;178770208 | chr2:179634937;179634936;179634935 |
| Novex-2 | 2785 | 8578;8579;8580 | chr2:178770210;178770209;178770208 | chr2:179634937;179634936;179634935 |
| Novex-3 | 2831 | 8716;8717;8718 | chr2:178770210;178770209;178770208 | chr2:179634937;179634936;179634935 |
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/N | rs2306636  |
0.014 | None | N | 0.079 | 0.138 | None | gnomAD-2.1.1 | 7.91051E-02 | None | None | None | None | N | None | 1.15767E-02 | 2.39204E-01 | None | 5.69388E-02 | 2.02128E-01 | None | 4.1057E-02 | None | 5.32999E-02 | 4.57174E-02 | 6.68145E-02 |
| S/N | rs2306636 |
0.014 | None | N | 0.079 | 0.138 | None | gnomAD-3.1.2 | 5.16731E-02 | None | None | None | None | N | None | 1.18726E-02 | 1.39565E-01 | 4.82456E-02 | 5.59723E-02 | 1.84913E-01 | None | 5.12361E-02 | 1.58228E-02 | 4.6592E-02 | 4.64345E-02 | 4.82792E-02 |
| S/N | rs2306636 |
0.014 | None | N | 0.079 | 0.138 | None | 1000 genomes | 8.127E-02 | None | None | None | None | N | None | 2.3E-03 | 1.729E-01 | None | None | 1.905E-01 | 5.07E-02 | None | None | None | 4.19E-02 | None |
| S/N | rs2306636 |
0.014 | None | N | 0.079 | 0.138 | None | gnomAD-4.0.0 | 5.47099E-02 | None | None | None | None | N | None | 1.09672E-02 | 2.05872E-01 | None | 5.52665E-02 | 1.92579E-01 | None | 5.40629E-02 | 1.96305E-02 | 4.57953E-02 | 4.17444E-02 | 5.42473E-02 |
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 | 0.0941 | likely_benign | 0.1047 | benign | -0.191 | Destabilizing | 0.001 | N | 0.159 | neutral | None | None | None | None | N |
| S/C | 0.1223 | likely_benign | 0.1399 | benign | -0.535 | Destabilizing | 0.258 | N | 0.401 | neutral | N | 0.451288688 | None | None | N |
| S/D | 0.0951 | likely_benign | 0.1136 | benign | 0.274 | Stabilizing | None | N | 0.175 | neutral | None | None | None | None | N |
| S/E | 0.2136 | likely_benign | 0.2677 | benign | 0.193 | Stabilizing | None | N | 0.173 | neutral | None | None | None | None | N |
| S/F | 0.3026 | likely_benign | 0.3583 | ambiguous | -0.927 | Destabilizing | 0.051 | N | 0.381 | neutral | None | None | None | None | N |
| S/G | 0.0632 | likely_benign | 0.0616 | benign | -0.253 | Destabilizing | None | N | 0.087 | neutral | N | 0.304732164 | None | None | N |
| S/H | 0.1207 | likely_benign | 0.1431 | benign | -0.445 | Destabilizing | 0.009 | N | 0.383 | neutral | None | None | None | None | N |
| S/I | 0.2125 | likely_benign | 0.2393 | benign | -0.161 | Destabilizing | 0.013 | N | 0.3 | neutral | N | 0.45414087 | None | None | N |
| S/K | 0.2203 | likely_benign | 0.2855 | benign | -0.277 | Destabilizing | None | N | 0.183 | neutral | None | None | None | None | N |
| S/L | 0.165 | likely_benign | 0.1921 | benign | -0.161 | Destabilizing | 0.002 | N | 0.297 | neutral | None | None | None | None | N |
| S/M | 0.1804 | likely_benign | 0.1931 | benign | -0.375 | Destabilizing | 0.116 | N | 0.449 | neutral | None | None | None | None | N |
| S/N | 0.0442 | likely_benign | 0.0438 | benign | -0.215 | Destabilizing | None | N | 0.079 | neutral | N | 0.345793846 | None | None | N |
| S/P | 0.5828 | likely_pathogenic | 0.6581 | pathogenic | -0.146 | Destabilizing | 0.008 | N | 0.304 | neutral | None | None | None | None | N |
| S/Q | 0.2083 | likely_benign | 0.2568 | benign | -0.347 | Destabilizing | 0.004 | N | 0.219 | neutral | None | None | None | None | N |
| S/R | 0.2302 | likely_benign | 0.2958 | benign | -0.036 | Destabilizing | 0.001 | N | 0.303 | neutral | N | 0.444652131 | None | None | N |
| S/T | 0.085 | likely_benign | 0.0887 | benign | -0.296 | Destabilizing | None | N | 0.177 | neutral | N | 0.448581409 | None | None | N |
| S/V | 0.222 | likely_benign | 0.2633 | benign | -0.146 | Destabilizing | 0.008 | N | 0.295 | neutral | None | None | None | None | N |
| S/W | 0.3887 | ambiguous | 0.4359 | ambiguous | -1.039 | Destabilizing | 0.316 | N | 0.462 | neutral | None | None | None | None | N |
| S/Y | 0.1434 | likely_benign | 0.1637 | benign | -0.693 | Destabilizing | 0.051 | N | 0.385 | 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.