Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35199 | 105820;105821;105822 | chr2:178531020;178531019;178531018 | chr2:179395747;179395746;179395745 |
| N2AB | 33558 | 100897;100898;100899 | chr2:178531020;178531019;178531018 | chr2:179395747;179395746;179395745 |
| N2A | 32631 | 98116;98117;98118 | chr2:178531020;178531019;178531018 | chr2:179395747;179395746;179395745 |
| N2B | 26134 | 78625;78626;78627 | chr2:178531020;178531019;178531018 | chr2:179395747;179395746;179395745 |
| Novex-1 | 26259 | 79000;79001;79002 | chr2:178531020;178531019;178531018 | chr2:179395747;179395746;179395745 |
| Novex-2 | 26326 | 79201;79202;79203 | chr2:178531020;178531019;178531018 | chr2:179395747;179395746;179395745 |
| 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 | rs759304538  |
-1.095 | 1.0 | D | 0.899 | 0.826 | 0.777932132617 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| Y/C | rs759304538 |
-1.095 | 1.0 | D | 0.899 | 0.826 | 0.777932132617 | gnomAD-4.0.0 | 1.59093E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85747E-06 | 0 | 0 |
| Y/H | rs1056456150 |
None | 0.999 | D | 0.795 | 0.815 | 0.632874758761 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/H | rs1056456150 |
None | 0.999 | D | 0.795 | 0.815 | 0.632874758761 | gnomAD-4.0.0 | 6.57566E-06 | None | None | None | None | N | None | 0 | 6.54965E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9875 | likely_pathogenic | 0.9879 | pathogenic | -1.329 | Destabilizing | 0.999 | D | 0.882 | deleterious | None | None | None | None | N |
| Y/C | 0.8035 | likely_pathogenic | 0.7989 | pathogenic | -0.806 | Destabilizing | 1.0 | D | 0.899 | deleterious | D | 0.662245653 | None | None | N |
| Y/D | 0.9912 | likely_pathogenic | 0.9924 | pathogenic | -2.245 | Highly Destabilizing | 0.999 | D | 0.907 | deleterious | D | 0.662245652 | None | None | N |
| Y/E | 0.9977 | likely_pathogenic | 0.9978 | pathogenic | -2.003 | Highly Destabilizing | 0.999 | D | 0.918 | deleterious | None | None | None | None | N |
| Y/F | 0.1803 | likely_benign | 0.181 | benign | -0.267 | Destabilizing | 0.997 | D | 0.671 | neutral | D | 0.591537233 | None | None | N |
| Y/G | 0.9803 | likely_pathogenic | 0.9822 | pathogenic | -1.755 | Destabilizing | 0.999 | D | 0.909 | deleterious | None | None | None | None | N |
| Y/H | 0.9312 | likely_pathogenic | 0.9387 | pathogenic | -1.705 | Destabilizing | 0.999 | D | 0.795 | deleterious | D | 0.662043848 | None | None | N |
| Y/I | 0.8959 | likely_pathogenic | 0.8745 | pathogenic | 0.063 | Stabilizing | 0.999 | D | 0.867 | deleterious | None | None | None | None | N |
| Y/K | 0.9974 | likely_pathogenic | 0.9971 | pathogenic | -1.1 | Destabilizing | 0.999 | D | 0.915 | deleterious | None | None | None | None | N |
| Y/L | 0.8387 | likely_pathogenic | 0.8181 | pathogenic | 0.063 | Stabilizing | 0.998 | D | 0.794 | deleterious | None | None | None | None | N |
| Y/M | 0.9706 | likely_pathogenic | 0.965 | pathogenic | -0.19 | Destabilizing | 1.0 | D | 0.86 | deleterious | None | None | None | None | N |
| Y/N | 0.9647 | likely_pathogenic | 0.9656 | pathogenic | -1.982 | Destabilizing | 0.999 | D | 0.911 | deleterious | D | 0.662245652 | None | None | N |
| Y/P | 0.9972 | likely_pathogenic | 0.9977 | pathogenic | -0.413 | Destabilizing | 0.999 | D | 0.923 | deleterious | None | None | None | None | N |
| Y/Q | 0.9962 | likely_pathogenic | 0.9962 | pathogenic | -1.463 | Destabilizing | 0.999 | D | 0.867 | deleterious | None | None | None | None | N |
| Y/R | 0.989 | likely_pathogenic | 0.9885 | pathogenic | -1.724 | Destabilizing | 0.999 | D | 0.915 | deleterious | None | None | None | None | N |
| Y/S | 0.9667 | likely_pathogenic | 0.968 | pathogenic | -2.174 | Highly Destabilizing | 0.999 | D | 0.915 | deleterious | D | 0.662245652 | None | None | N |
| Y/T | 0.983 | likely_pathogenic | 0.982 | pathogenic | -1.781 | Destabilizing | 0.999 | D | 0.916 | deleterious | None | None | None | None | N |
| Y/V | 0.8463 | likely_pathogenic | 0.8266 | pathogenic | -0.413 | Destabilizing | 0.999 | D | 0.839 | deleterious | None | None | None | None | N |
| Y/W | 0.7264 | likely_pathogenic | 0.7595 | pathogenic | 0.212 | Stabilizing | 1.0 | D | 0.785 | 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.