Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21683 | 65272;65273;65274 | chr2:178584504;178584503;178584502 | chr2:179449231;179449230;179449229 |
| N2AB | 20042 | 60349;60350;60351 | chr2:178584504;178584503;178584502 | chr2:179449231;179449230;179449229 |
| N2A | 19115 | 57568;57569;57570 | chr2:178584504;178584503;178584502 | chr2:179449231;179449230;179449229 |
| N2B | 12618 | 38077;38078;38079 | chr2:178584504;178584503;178584502 | chr2:179449231;179449230;179449229 |
| Novex-1 | 12743 | 38452;38453;38454 | chr2:178584504;178584503;178584502 | chr2:179449231;179449230;179449229 |
| Novex-2 | 12810 | 38653;38654;38655 | chr2:178584504;178584503;178584502 | chr2:179449231;179449230;179449229 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs1328998714  |
None | 1.0 | D | 0.907 | 0.553 | 0.81331731886 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/L | rs1328998714 |
None | 1.0 | D | 0.907 | 0.553 | 0.81331731886 | gnomAD-4.0.0 | 1.2399E-06 | None | None | None | None | N | None | 1.33622E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.09815E-05 | 0 |
| P/Q | rs1328998714 |
None | 1.0 | D | 0.859 | 0.548 | 0.669752846865 | gnomAD-4.0.0 | 2.05332E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 3.47464E-04 | 8.99643E-07 | 0 | 0 |
| P/T | rs528707403 |
-2.085 | 1.0 | D | 0.866 | 0.541 | 0.650379344195 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 5.34E-05 | 0 |
| P/T | rs528707403 |
-2.085 | 1.0 | D | 0.866 | 0.541 | 0.650379344195 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.36E-05 | 0 | 0 |
| P/T | rs528707403 |
-2.085 | 1.0 | D | 0.866 | 0.541 | 0.650379344195 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| P/T | rs528707403 |
-2.085 | 1.0 | D | 0.866 | 0.541 | 0.650379344195 | gnomAD-4.0.0 | 1.35759E-04 | None | None | None | None | N | None | 1.33429E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.82278E-04 | 0 | 4.80446E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.8551 | likely_pathogenic | 0.8811 | pathogenic | -2.123 | Highly Destabilizing | 1.0 | D | 0.829 | deleterious | D | 0.574399923 | None | None | N |
| P/C | 0.9808 | likely_pathogenic | 0.9812 | pathogenic | -1.64 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| P/D | 0.9976 | likely_pathogenic | 0.9981 | pathogenic | -2.456 | Highly Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| P/E | 0.9952 | likely_pathogenic | 0.9961 | pathogenic | -2.391 | Highly Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| P/F | 0.9993 | likely_pathogenic | 0.9995 | pathogenic | -1.595 | Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | N |
| P/G | 0.9799 | likely_pathogenic | 0.9825 | pathogenic | -2.531 | Highly Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | None | N |
| P/H | 0.9947 | likely_pathogenic | 0.9954 | pathogenic | -2.079 | Highly Destabilizing | 1.0 | D | 0.885 | deleterious | None | None | None | None | N |
| P/I | 0.9931 | likely_pathogenic | 0.9947 | pathogenic | -1.047 | Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | None | N |
| P/K | 0.9976 | likely_pathogenic | 0.9981 | pathogenic | -1.83 | Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| P/L | 0.9747 | likely_pathogenic | 0.9772 | pathogenic | -1.047 | Destabilizing | 1.0 | D | 0.907 | deleterious | D | 0.62971583 | None | None | N |
| P/M | 0.9941 | likely_pathogenic | 0.9953 | pathogenic | -0.815 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| P/N | 0.9967 | likely_pathogenic | 0.9975 | pathogenic | -1.773 | Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | N |
| P/Q | 0.9931 | likely_pathogenic | 0.9946 | pathogenic | -1.887 | Destabilizing | 1.0 | D | 0.859 | deleterious | D | 0.614705491 | None | None | N |
| P/R | 0.9937 | likely_pathogenic | 0.9943 | pathogenic | -1.301 | Destabilizing | 1.0 | D | 0.9 | deleterious | D | 0.630523047 | None | None | N |
| P/S | 0.9661 | likely_pathogenic | 0.9746 | pathogenic | -2.336 | Highly Destabilizing | 1.0 | D | 0.866 | deleterious | D | 0.543118415 | None | None | N |
| P/T | 0.9545 | likely_pathogenic | 0.9654 | pathogenic | -2.152 | Highly Destabilizing | 1.0 | D | 0.866 | deleterious | D | 0.592942734 | None | None | N |
| P/V | 0.9767 | likely_pathogenic | 0.9809 | pathogenic | -1.375 | Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | None | N |
| P/W | 0.9995 | likely_pathogenic | 0.9996 | pathogenic | -1.884 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| P/Y | 0.9993 | likely_pathogenic | 0.9995 | pathogenic | -1.616 | Destabilizing | 1.0 | D | 0.905 | 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.