Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18048 | 54367;54368;54369 | chr2:178605035;178605034;178605033 | chr2:179469762;179469761;179469760 |
| N2AB | 16407 | 49444;49445;49446 | chr2:178605035;178605034;178605033 | chr2:179469762;179469761;179469760 |
| N2A | 15480 | 46663;46664;46665 | chr2:178605035;178605034;178605033 | chr2:179469762;179469761;179469760 |
| N2B | 8983 | 27172;27173;27174 | chr2:178605035;178605034;178605033 | chr2:179469762;179469761;179469760 |
| Novex-1 | 9108 | 27547;27548;27549 | chr2:178605035;178605034;178605033 | chr2:179469762;179469761;179469760 |
| Novex-2 | 9175 | 27748;27749;27750 | chr2:178605035;178605034;178605033 | chr2:179469762;179469761;179469760 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/P | rs878999356  |
-0.369 | 0.638 | N | 0.761 | 0.48 | None | gnomAD-2.1.1 | 1.63E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.6E-05 | 0 |
| S/P | rs878999356 |
-0.369 | 0.638 | N | 0.761 | 0.48 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.42E-05 | 0 | 0 |
| S/P | rs878999356 |
-0.369 | 0.638 | N | 0.761 | 0.48 | None | gnomAD-4.0.0 | 6.28136E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.13293E-05 | 0 | 8.16204E-05 | 0 | 4.82176E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1012 | likely_benign | 0.1018 | benign | -0.574 | Destabilizing | 0.002 | N | 0.269 | neutral | D | 0.522322475 | None | None | I |
| S/C | 0.1752 | likely_benign | 0.1622 | benign | -0.454 | Destabilizing | 0.931 | D | 0.757 | deleterious | N | 0.503711814 | None | None | I |
| S/D | 0.6854 | likely_pathogenic | 0.7049 | pathogenic | -0.637 | Destabilizing | 0.399 | N | 0.679 | prob.neutral | None | None | None | None | I |
| S/E | 0.6205 | likely_pathogenic | 0.6445 | pathogenic | -0.7 | Destabilizing | 0.399 | N | 0.659 | neutral | None | None | None | None | I |
| S/F | 0.2797 | likely_benign | 0.2628 | benign | -1.116 | Destabilizing | 0.781 | D | 0.839 | deleterious | N | 0.489886746 | None | None | I |
| S/G | 0.1493 | likely_benign | 0.1536 | benign | -0.725 | Destabilizing | 0.25 | N | 0.572 | neutral | None | None | None | None | I |
| S/H | 0.3962 | ambiguous | 0.3937 | ambiguous | -1.365 | Destabilizing | 0.982 | D | 0.752 | deleterious | None | None | None | None | I |
| S/I | 0.2639 | likely_benign | 0.2342 | benign | -0.292 | Destabilizing | 0.7 | D | 0.826 | deleterious | None | None | None | None | I |
| S/K | 0.714 | likely_pathogenic | 0.7186 | pathogenic | -0.686 | Destabilizing | 0.399 | N | 0.656 | neutral | None | None | None | None | I |
| S/L | 0.1708 | likely_benign | 0.1547 | benign | -0.292 | Destabilizing | 0.25 | N | 0.71 | prob.delet. | None | None | None | None | I |
| S/M | 0.2238 | likely_benign | 0.2072 | benign | 0.195 | Stabilizing | 0.947 | D | 0.753 | deleterious | None | None | None | None | I |
| S/N | 0.2184 | likely_benign | 0.1942 | benign | -0.569 | Destabilizing | 0.826 | D | 0.701 | prob.neutral | None | None | None | None | I |
| S/P | 0.986 | likely_pathogenic | 0.9851 | pathogenic | -0.357 | Destabilizing | 0.638 | D | 0.761 | deleterious | N | 0.521562579 | None | None | I |
| S/Q | 0.4903 | ambiguous | 0.501 | ambiguous | -0.909 | Destabilizing | 0.826 | D | 0.74 | deleterious | None | None | None | None | I |
| S/R | 0.6569 | likely_pathogenic | 0.6639 | pathogenic | -0.443 | Destabilizing | 0.7 | D | 0.768 | deleterious | None | None | None | None | I |
| S/T | 0.0692 | likely_benign | 0.0664 | benign | -0.59 | Destabilizing | 0.201 | N | 0.571 | neutral | N | 0.445821775 | None | None | I |
| S/V | 0.2156 | likely_benign | 0.2023 | benign | -0.357 | Destabilizing | 0.539 | D | 0.745 | deleterious | None | None | None | None | I |
| S/W | 0.5216 | ambiguous | 0.5347 | ambiguous | -1.09 | Destabilizing | 0.982 | D | 0.809 | deleterious | None | None | None | None | I |
| S/Y | 0.3178 | likely_benign | 0.3006 | benign | -0.811 | Destabilizing | 0.781 | D | 0.837 | deleterious | N | 0.503458324 | 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.