Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28882 | 86869;86870;86871 | chr2:178559488;178559487;178559486 | chr2:179424215;179424214;179424213 |
| N2AB | 27241 | 81946;81947;81948 | chr2:178559488;178559487;178559486 | chr2:179424215;179424214;179424213 |
| N2A | 26314 | 79165;79166;79167 | chr2:178559488;178559487;178559486 | chr2:179424215;179424214;179424213 |
| N2B | 19817 | 59674;59675;59676 | chr2:178559488;178559487;178559486 | chr2:179424215;179424214;179424213 |
| Novex-1 | 19942 | 60049;60050;60051 | chr2:178559488;178559487;178559486 | chr2:179424215;179424214;179424213 |
| Novex-2 | 20009 | 60250;60251;60252 | chr2:178559488;178559487;178559486 | chr2:179424215;179424214;179424213 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs374491926  |
-3.286 | 0.722 | N | 0.607 | 0.501 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs374491926 |
-3.286 | 0.722 | N | 0.607 | 0.501 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs374491926 |
-3.286 | 0.722 | N | 0.607 | 0.501 | None | gnomAD-4.0.0 | 3.71866E-06 | None | None | None | None | N | None | 5.34359E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47669E-07 | 1.09813E-05 | 0 |
| I/V | None | None | 0.001 | N | 0.207 | 0.066 | 0.327952845175 | gnomAD-4.0.0 | 1.36848E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79903E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8369 | likely_pathogenic | 0.83 | pathogenic | -2.922 | Highly Destabilizing | 0.415 | N | 0.645 | neutral | None | None | None | None | N |
| I/C | 0.9467 | likely_pathogenic | 0.9459 | pathogenic | -2.17 | Highly Destabilizing | 0.989 | D | 0.78 | deleterious | None | None | None | None | N |
| I/D | 0.9995 | likely_pathogenic | 0.9995 | pathogenic | -3.516 | Highly Destabilizing | 0.987 | D | 0.863 | deleterious | None | None | None | None | N |
| I/E | 0.9977 | likely_pathogenic | 0.9978 | pathogenic | -3.182 | Highly Destabilizing | 0.961 | D | 0.843 | deleterious | None | None | None | None | N |
| I/F | 0.7512 | likely_pathogenic | 0.757 | pathogenic | -1.646 | Destabilizing | 0.923 | D | 0.643 | neutral | None | None | None | None | N |
| I/G | 0.9904 | likely_pathogenic | 0.9905 | pathogenic | -3.549 | Highly Destabilizing | 0.961 | D | 0.812 | deleterious | None | None | None | None | N |
| I/H | 0.9976 | likely_pathogenic | 0.9977 | pathogenic | -3.193 | Highly Destabilizing | 0.996 | D | 0.869 | deleterious | None | None | None | None | N |
| I/K | 0.9955 | likely_pathogenic | 0.9957 | pathogenic | -2.118 | Highly Destabilizing | 0.949 | D | 0.847 | deleterious | N | 0.518112177 | None | None | N |
| I/L | 0.2687 | likely_benign | 0.2493 | benign | -1.022 | Destabilizing | 0.19 | N | 0.321 | neutral | N | 0.485795954 | None | None | N |
| I/M | 0.3442 | ambiguous | 0.3471 | ambiguous | -1.319 | Destabilizing | 0.901 | D | 0.629 | neutral | N | 0.479750847 | None | None | N |
| I/N | 0.9946 | likely_pathogenic | 0.9949 | pathogenic | -2.839 | Highly Destabilizing | 0.987 | D | 0.873 | deleterious | None | None | None | None | N |
| I/P | 0.9947 | likely_pathogenic | 0.9948 | pathogenic | -1.648 | Destabilizing | 0.987 | D | 0.868 | deleterious | None | None | None | None | N |
| I/Q | 0.9959 | likely_pathogenic | 0.9961 | pathogenic | -2.466 | Highly Destabilizing | 0.987 | D | 0.881 | deleterious | None | None | None | None | N |
| I/R | 0.9923 | likely_pathogenic | 0.9923 | pathogenic | -2.197 | Highly Destabilizing | 0.949 | D | 0.872 | deleterious | N | 0.518112177 | None | None | N |
| I/S | 0.9719 | likely_pathogenic | 0.9719 | pathogenic | -3.419 | Highly Destabilizing | 0.923 | D | 0.769 | deleterious | None | None | None | None | N |
| I/T | 0.7381 | likely_pathogenic | 0.7389 | pathogenic | -2.916 | Highly Destabilizing | 0.722 | D | 0.607 | neutral | N | 0.517858687 | None | None | N |
| I/V | 0.0677 | likely_benign | 0.0688 | benign | -1.648 | Destabilizing | 0.001 | N | 0.207 | neutral | N | 0.386988823 | None | None | N |
| I/W | 0.9957 | likely_pathogenic | 0.9957 | pathogenic | -2.026 | Highly Destabilizing | 0.996 | D | 0.853 | deleterious | None | None | None | None | N |
| I/Y | 0.9879 | likely_pathogenic | 0.9877 | pathogenic | -1.872 | Destabilizing | 0.961 | D | 0.743 | deleterious | 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.