Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28717 | 86374;86375;86376 | chr2:178559983;178559982;178559981 | chr2:179424710;179424709;179424708 |
| N2AB | 27076 | 81451;81452;81453 | chr2:178559983;178559982;178559981 | chr2:179424710;179424709;179424708 |
| N2A | 26149 | 78670;78671;78672 | chr2:178559983;178559982;178559981 | chr2:179424710;179424709;179424708 |
| N2B | 19652 | 59179;59180;59181 | chr2:178559983;178559982;178559981 | chr2:179424710;179424709;179424708 |
| Novex-1 | 19777 | 59554;59555;59556 | chr2:178559983;178559982;178559981 | chr2:179424710;179424709;179424708 |
| Novex-2 | 19844 | 59755;59756;59757 | chr2:178559983;178559982;178559981 | chr2:179424710;179424709;179424708 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs757567360  |
-0.506 | None | N | 0.045 | 0.037 | 0.0762999501168 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.30745E-04 | None | 0 | 0 | 0 |
| T/A | rs757567360 |
-0.506 | None | N | 0.045 | 0.037 | 0.0762999501168 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78469E-04 |
| T/A | rs757567360 |
-0.506 | None | N | 0.045 | 0.037 | 0.0762999501168 | gnomAD-4.0.0 | 7.43644E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47587E-07 | 9.88121E-05 | 3.20215E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0572 | likely_benign | 0.0566 | benign | -0.519 | Destabilizing | None | N | 0.045 | neutral | N | 0.411849982 | None | None | N |
| T/C | 0.2935 | likely_benign | 0.3117 | benign | -0.221 | Destabilizing | 0.667 | D | 0.4 | neutral | None | None | None | None | N |
| T/D | 0.2927 | likely_benign | 0.3243 | benign | -0.104 | Destabilizing | 0.22 | N | 0.329 | neutral | None | None | None | None | N |
| T/E | 0.2186 | likely_benign | 0.2454 | benign | -0.192 | Destabilizing | 0.055 | N | 0.309 | neutral | None | None | None | None | N |
| T/F | 0.1948 | likely_benign | 0.2229 | benign | -1.083 | Destabilizing | 0.667 | D | 0.395 | neutral | None | None | None | None | N |
| T/G | 0.1731 | likely_benign | 0.1711 | benign | -0.628 | Destabilizing | 0.055 | N | 0.225 | neutral | None | None | None | None | N |
| T/H | 0.2105 | likely_benign | 0.2393 | benign | -1.027 | Destabilizing | 0.667 | D | 0.4 | neutral | None | None | None | None | N |
| T/I | 0.1201 | likely_benign | 0.1374 | benign | -0.347 | Destabilizing | 0.175 | N | 0.456 | neutral | N | 0.445869342 | None | None | N |
| T/K | 0.2095 | likely_benign | 0.2381 | benign | -0.372 | Destabilizing | 0.042 | N | 0.319 | neutral | N | 0.424896637 | None | None | N |
| T/L | 0.079 | likely_benign | 0.0879 | benign | -0.347 | Destabilizing | 0.104 | N | 0.309 | neutral | None | None | None | None | N |
| T/M | 0.077 | likely_benign | 0.0873 | benign | 0.086 | Stabilizing | 0.859 | D | 0.396 | neutral | None | None | None | None | N |
| T/N | 0.1038 | likely_benign | 0.1104 | benign | -0.145 | Destabilizing | 0.124 | N | 0.354 | neutral | None | None | None | None | N |
| T/P | 0.067 | likely_benign | 0.0685 | benign | -0.378 | Destabilizing | None | N | 0.088 | neutral | N | 0.309903758 | None | None | N |
| T/Q | 0.1895 | likely_benign | 0.2105 | benign | -0.478 | Destabilizing | 0.22 | N | 0.449 | neutral | None | None | None | None | N |
| T/R | 0.177 | likely_benign | 0.2025 | benign | -0.059 | Destabilizing | 0.175 | N | 0.448 | neutral | N | 0.454142109 | None | None | N |
| T/S | 0.0818 | likely_benign | 0.0849 | benign | -0.343 | Destabilizing | None | N | 0.039 | neutral | N | 0.381433861 | None | None | N |
| T/V | 0.0943 | likely_benign | 0.1042 | benign | -0.378 | Destabilizing | 0.104 | N | 0.323 | neutral | None | None | None | None | N |
| T/W | 0.5157 | ambiguous | 0.5674 | pathogenic | -1.039 | Destabilizing | 0.958 | D | 0.389 | neutral | None | None | None | None | N |
| T/Y | 0.2228 | likely_benign | 0.2388 | benign | -0.768 | Destabilizing | 0.667 | D | 0.395 | 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.