Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28150 | 84673;84674;84675 | chr2:178561684;178561683;178561682 | chr2:179426411;179426410;179426409 |
| N2AB | 26509 | 79750;79751;79752 | chr2:178561684;178561683;178561682 | chr2:179426411;179426410;179426409 |
| N2A | 25582 | 76969;76970;76971 | chr2:178561684;178561683;178561682 | chr2:179426411;179426410;179426409 |
| N2B | 19085 | 57478;57479;57480 | chr2:178561684;178561683;178561682 | chr2:179426411;179426410;179426409 |
| Novex-1 | 19210 | 57853;57854;57855 | chr2:178561684;178561683;178561682 | chr2:179426411;179426410;179426409 |
| Novex-2 | 19277 | 58054;58055;58056 | chr2:178561684;178561683;178561682 | chr2:179426411;179426410;179426409 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | None | None | 1.0 | N | 0.769 | 0.274 | 0.575279034457 | gnomAD-4.0.0 | 1.60752E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.89064E-06 | 0 | 0 |
| Y/H | rs397517727  |
0.596 | 1.0 | N | 0.645 | 0.212 | 0.377976839388 | gnomAD-2.1.1 | 9.83E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 8.10975E-04 | None | 0 | 0 | 0 |
| Y/H | rs397517727 |
0.596 | 1.0 | N | 0.645 | 0.212 | 0.377976839388 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.14079E-04 | 0 |
| Y/H | rs397517727 |
0.596 | 1.0 | N | 0.645 | 0.212 | 0.377976839388 | 1000 genomes | 3.99361E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 2E-03 | None |
| Y/H | rs397517727 |
0.596 | 1.0 | N | 0.645 | 0.212 | 0.377976839388 | gnomAD-4.0.0 | 3.73312E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.66058E-04 | 0 | 6.20059E-04 | 4.82455E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9142 | likely_pathogenic | 0.9252 | pathogenic | -0.7 | Destabilizing | 0.997 | D | 0.479 | neutral | None | None | None | None | I |
| Y/C | 0.6732 | likely_pathogenic | 0.6965 | pathogenic | 0.215 | Stabilizing | 1.0 | D | 0.769 | deleterious | N | 0.471894855 | None | None | I |
| Y/D | 0.6818 | likely_pathogenic | 0.7866 | pathogenic | 0.855 | Stabilizing | 1.0 | D | 0.749 | deleterious | N | 0.41881324 | None | None | I |
| Y/E | 0.9526 | likely_pathogenic | 0.9623 | pathogenic | 0.837 | Stabilizing | 1.0 | D | 0.706 | prob.delet. | None | None | None | None | I |
| Y/F | 0.2065 | likely_benign | 0.2102 | benign | -0.373 | Destabilizing | 0.262 | N | 0.347 | neutral | N | 0.520630886 | None | None | I |
| Y/G | 0.8986 | likely_pathogenic | 0.9123 | pathogenic | -0.896 | Destabilizing | 1.0 | D | 0.733 | deleterious | None | None | None | None | I |
| Y/H | 0.4533 | ambiguous | 0.4957 | ambiguous | 0.136 | Stabilizing | 1.0 | D | 0.645 | neutral | N | 0.477437469 | None | None | I |
| Y/I | 0.8821 | likely_pathogenic | 0.9021 | pathogenic | -0.201 | Destabilizing | 0.998 | D | 0.605 | neutral | None | None | None | None | I |
| Y/K | 0.9339 | likely_pathogenic | 0.9384 | pathogenic | 0.229 | Stabilizing | 1.0 | D | 0.704 | prob.delet. | None | None | None | None | I |
| Y/L | 0.6875 | likely_pathogenic | 0.7121 | pathogenic | -0.201 | Destabilizing | 0.987 | D | 0.58 | neutral | None | None | None | None | I |
| Y/M | 0.862 | likely_pathogenic | 0.8835 | pathogenic | -0.019 | Destabilizing | 1.0 | D | 0.597 | neutral | None | None | None | None | I |
| Y/N | 0.4647 | ambiguous | 0.5263 | ambiguous | 0.081 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | N | 0.473839803 | None | None | I |
| Y/P | 0.9417 | likely_pathogenic | 0.9463 | pathogenic | -0.348 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| Y/Q | 0.9344 | likely_pathogenic | 0.9429 | pathogenic | 0.117 | Stabilizing | 1.0 | D | 0.607 | neutral | None | None | None | None | I |
| Y/R | 0.9217 | likely_pathogenic | 0.9263 | pathogenic | 0.478 | Stabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| Y/S | 0.7111 | likely_pathogenic | 0.7582 | pathogenic | -0.343 | Destabilizing | 1.0 | D | 0.7 | prob.delet. | N | 0.479957699 | None | None | I |
| Y/T | 0.9213 | likely_pathogenic | 0.9335 | pathogenic | -0.267 | Destabilizing | 1.0 | D | 0.706 | prob.delet. | None | None | None | None | I |
| Y/V | 0.8608 | likely_pathogenic | 0.8811 | pathogenic | -0.348 | Destabilizing | 0.993 | D | 0.576 | neutral | None | None | None | None | I |
| Y/W | 0.6947 | likely_pathogenic | 0.729 | pathogenic | -0.496 | Destabilizing | 1.0 | D | 0.623 | neutral | None | None | 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.