Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24923 | 74992;74993;74994 | chr2:178571365;178571364;178571363 | chr2:179436092;179436091;179436090 |
| N2AB | 23282 | 70069;70070;70071 | chr2:178571365;178571364;178571363 | chr2:179436092;179436091;179436090 |
| N2A | 22355 | 67288;67289;67290 | chr2:178571365;178571364;178571363 | chr2:179436092;179436091;179436090 |
| N2B | 15858 | 47797;47798;47799 | chr2:178571365;178571364;178571363 | chr2:179436092;179436091;179436090 |
| Novex-1 | 15983 | 48172;48173;48174 | chr2:178571365;178571364;178571363 | chr2:179436092;179436091;179436090 |
| Novex-2 | 16050 | 48373;48374;48375 | chr2:178571365;178571364;178571363 | chr2:179436092;179436091;179436090 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/H | None | None | 1.0 | D | 0.619 | 0.406 | 0.378674557249 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 0 |
| D/N | None | None | 0.989 | N | 0.513 | 0.254 | 0.325263233342 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.246 | likely_benign | 0.2367 | benign | -0.505 | Destabilizing | 0.978 | D | 0.553 | neutral | N | 0.475941142 | None | None | N |
| D/C | 0.5933 | likely_pathogenic | 0.5982 | pathogenic | 0.154 | Stabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| D/E | 0.1331 | likely_benign | 0.1385 | benign | -0.523 | Destabilizing | 0.198 | N | 0.143 | neutral | N | 0.464975178 | None | None | N |
| D/F | 0.5103 | ambiguous | 0.498 | ambiguous | -0.929 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| D/G | 0.2177 | likely_benign | 0.2015 | benign | -0.68 | Destabilizing | 0.989 | D | 0.54 | neutral | N | 0.517404153 | None | None | N |
| D/H | 0.3396 | likely_benign | 0.3286 | benign | -1.128 | Destabilizing | 1.0 | D | 0.619 | neutral | D | 0.524215482 | None | None | N |
| D/I | 0.3928 | ambiguous | 0.3868 | ambiguous | -0.089 | Destabilizing | 0.999 | D | 0.728 | prob.delet. | None | None | None | None | N |
| D/K | 0.4952 | ambiguous | 0.4761 | ambiguous | 0.254 | Stabilizing | 0.983 | D | 0.541 | neutral | None | None | None | None | N |
| D/L | 0.396 | ambiguous | 0.3874 | ambiguous | -0.089 | Destabilizing | 0.998 | D | 0.728 | prob.delet. | None | None | None | None | N |
| D/M | 0.5657 | likely_pathogenic | 0.5801 | pathogenic | 0.391 | Stabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| D/N | 0.0993 | likely_benign | 0.0995 | benign | 0.078 | Stabilizing | 0.989 | D | 0.513 | neutral | N | 0.492254993 | None | None | N |
| D/P | 0.9303 | likely_pathogenic | 0.921 | pathogenic | -0.208 | Destabilizing | 0.999 | D | 0.635 | neutral | None | None | None | None | N |
| D/Q | 0.3608 | ambiguous | 0.3625 | ambiguous | 0.049 | Stabilizing | 0.995 | D | 0.559 | neutral | None | None | None | None | N |
| D/R | 0.5497 | ambiguous | 0.5231 | ambiguous | 0.083 | Stabilizing | 0.995 | D | 0.705 | prob.neutral | None | None | None | None | N |
| D/S | 0.1456 | likely_benign | 0.1445 | benign | -0.05 | Destabilizing | 0.983 | D | 0.453 | neutral | None | None | None | None | N |
| D/T | 0.223 | likely_benign | 0.2229 | benign | 0.094 | Stabilizing | 0.998 | D | 0.575 | neutral | None | None | None | None | N |
| D/V | 0.2571 | likely_benign | 0.249 | benign | -0.208 | Destabilizing | 0.997 | D | 0.73 | prob.delet. | N | 0.519644843 | None | None | N |
| D/W | 0.8773 | likely_pathogenic | 0.8696 | pathogenic | -0.909 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| D/Y | 0.2362 | likely_benign | 0.2191 | benign | -0.709 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | N | 0.481537002 | 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.