Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31841 | 95746;95747;95748 | chr2:178545589;178545588;178545587 | chr2:179410316;179410315;179410314 |
| N2AB | 30200 | 90823;90824;90825 | chr2:178545589;178545588;178545587 | chr2:179410316;179410315;179410314 |
| N2A | 29273 | 88042;88043;88044 | chr2:178545589;178545588;178545587 | chr2:179410316;179410315;179410314 |
| N2B | 22776 | 68551;68552;68553 | chr2:178545589;178545588;178545587 | chr2:179410316;179410315;179410314 |
| Novex-1 | 22901 | 68926;68927;68928 | chr2:178545589;178545588;178545587 | chr2:179410316;179410315;179410314 |
| Novex-2 | 22968 | 69127;69128;69129 | chr2:178545589;178545588;178545587 | chr2:179410316;179410315;179410314 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/D | rs794729540  |
-1.199 | 0.008 | N | 0.431 | 0.163 | None | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| N/D | rs794729540 |
-1.199 | 0.008 | N | 0.431 | 0.163 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| N/D | rs794729540 |
-1.199 | 0.008 | N | 0.431 | 0.163 | None | gnomAD-4.0.0 | 1.6732E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.28866E-05 | 0 | 0 |
| N/Y | None | None | 0.983 | N | 0.765 | 0.402 | 0.329020015101 | gnomAD-4.0.0 | 6.84233E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99514E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.2645 | likely_benign | 0.2735 | benign | -1.288 | Destabilizing | 0.633 | D | 0.755 | deleterious | None | None | None | None | N |
| N/C | 0.2289 | likely_benign | 0.2151 | benign | -0.226 | Destabilizing | 0.996 | D | 0.811 | deleterious | None | None | None | None | N |
| N/D | 0.2048 | likely_benign | 0.2524 | benign | -0.742 | Destabilizing | 0.008 | N | 0.431 | neutral | N | 0.511150185 | None | None | N |
| N/E | 0.5922 | likely_pathogenic | 0.6356 | pathogenic | -0.532 | Destabilizing | 0.633 | D | 0.629 | neutral | None | None | None | None | N |
| N/F | 0.5638 | ambiguous | 0.5597 | ambiguous | -0.708 | Destabilizing | 0.961 | D | 0.827 | deleterious | None | None | None | None | N |
| N/G | 0.2371 | likely_benign | 0.2428 | benign | -1.69 | Destabilizing | 0.775 | D | 0.601 | neutral | None | None | None | None | N |
| N/H | 0.1114 | likely_benign | 0.1042 | benign | -0.834 | Destabilizing | 0.983 | D | 0.613 | neutral | N | 0.468860845 | None | None | N |
| N/I | 0.4948 | ambiguous | 0.5095 | ambiguous | -0.209 | Destabilizing | 0.82 | D | 0.829 | deleterious | N | 0.484891137 | None | None | N |
| N/K | 0.4815 | ambiguous | 0.5028 | ambiguous | 0.041 | Stabilizing | 0.722 | D | 0.655 | neutral | N | 0.492524352 | None | None | N |
| N/L | 0.3564 | ambiguous | 0.3399 | benign | -0.209 | Destabilizing | 0.858 | D | 0.807 | deleterious | None | None | None | None | N |
| N/M | 0.4508 | ambiguous | 0.4336 | ambiguous | 0.044 | Stabilizing | 0.989 | D | 0.745 | deleterious | None | None | None | None | N |
| N/P | 0.9312 | likely_pathogenic | 0.9377 | pathogenic | -0.543 | Destabilizing | 0.961 | D | 0.769 | deleterious | None | None | None | None | N |
| N/Q | 0.4132 | ambiguous | 0.4146 | ambiguous | -0.516 | Destabilizing | 0.961 | D | 0.628 | neutral | None | None | None | None | N |
| N/R | 0.4302 | ambiguous | 0.4484 | ambiguous | 0.012 | Stabilizing | 0.923 | D | 0.627 | neutral | None | None | None | None | N |
| N/S | 0.0755 | likely_benign | 0.0789 | benign | -0.983 | Destabilizing | 0.349 | N | 0.603 | neutral | N | 0.489830763 | None | None | N |
| N/T | 0.1385 | likely_benign | 0.14 | benign | -0.56 | Destabilizing | 0.008 | N | 0.273 | neutral | N | 0.495084654 | None | None | N |
| N/V | 0.4166 | ambiguous | 0.4318 | ambiguous | -0.543 | Destabilizing | 0.858 | D | 0.802 | deleterious | None | None | None | None | N |
| N/W | 0.8263 | likely_pathogenic | 0.8266 | pathogenic | -0.339 | Destabilizing | 0.996 | D | 0.769 | deleterious | None | None | None | None | N |
| N/Y | 0.2181 | likely_benign | 0.208 | benign | -0.108 | Destabilizing | 0.983 | D | 0.765 | deleterious | N | 0.504320213 | 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.