Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23663 | 71212;71213;71214 | chr2:178575145;178575144;178575143 | chr2:179439872;179439871;179439870 |
| N2AB | 22022 | 66289;66290;66291 | chr2:178575145;178575144;178575143 | chr2:179439872;179439871;179439870 |
| N2A | 21095 | 63508;63509;63510 | chr2:178575145;178575144;178575143 | chr2:179439872;179439871;179439870 |
| N2B | 14598 | 44017;44018;44019 | chr2:178575145;178575144;178575143 | chr2:179439872;179439871;179439870 |
| Novex-1 | 14723 | 44392;44393;44394 | chr2:178575145;178575144;178575143 | chr2:179439872;179439871;179439870 |
| Novex-2 | 14790 | 44593;44594;44595 | chr2:178575145;178575144;178575143 | chr2:179439872;179439871;179439870 |
| 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/A | rs1709593893  |
None | 1.0 | D | 0.793 | 0.735 | 0.52360052443 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/A | rs1709593893 |
None | 1.0 | D | 0.793 | 0.735 | 0.52360052443 | gnomAD-4.0.0 | 3.72069E-06 | None | None | None | None | I | None | 2.67158E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 6.40985E-05 |
| P/L | None | None | 1.0 | D | 0.817 | 0.762 | 0.698655912635 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.627 | likely_pathogenic | 0.6395 | pathogenic | -1.253 | Destabilizing | 1.0 | D | 0.793 | deleterious | D | 0.522712485 | None | None | I |
| P/C | 0.9764 | likely_pathogenic | 0.9768 | pathogenic | -0.809 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | I |
| P/D | 0.9988 | likely_pathogenic | 0.9987 | pathogenic | -1.276 | Destabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | I |
| P/E | 0.9967 | likely_pathogenic | 0.9965 | pathogenic | -1.36 | Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | I |
| P/F | 0.9983 | likely_pathogenic | 0.9981 | pathogenic | -1.315 | Destabilizing | 1.0 | D | 0.788 | deleterious | None | None | None | None | I |
| P/G | 0.9725 | likely_pathogenic | 0.9739 | pathogenic | -1.471 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | I |
| P/H | 0.9962 | likely_pathogenic | 0.996 | pathogenic | -1.106 | Destabilizing | 1.0 | D | 0.766 | deleterious | D | 0.568835723 | None | None | I |
| P/I | 0.9597 | likely_pathogenic | 0.9603 | pathogenic | -0.786 | Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | I |
| P/K | 0.998 | likely_pathogenic | 0.998 | pathogenic | -1.05 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | I |
| P/L | 0.9218 | likely_pathogenic | 0.9228 | pathogenic | -0.786 | Destabilizing | 1.0 | D | 0.817 | deleterious | D | 0.563765932 | None | None | I |
| P/M | 0.9784 | likely_pathogenic | 0.9791 | pathogenic | -0.479 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | I |
| P/N | 0.9968 | likely_pathogenic | 0.9967 | pathogenic | -0.732 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | I |
| P/Q | 0.9927 | likely_pathogenic | 0.9924 | pathogenic | -1.029 | Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | I |
| P/R | 0.9945 | likely_pathogenic | 0.9942 | pathogenic | -0.445 | Destabilizing | 1.0 | D | 0.835 | deleterious | D | 0.568328744 | None | None | I |
| P/S | 0.9649 | likely_pathogenic | 0.9665 | pathogenic | -1.113 | Destabilizing | 1.0 | D | 0.836 | deleterious | D | 0.556465459 | None | None | I |
| P/T | 0.9491 | likely_pathogenic | 0.9509 | pathogenic | -1.104 | Destabilizing | 1.0 | D | 0.832 | deleterious | D | 0.54971751 | None | None | I |
| P/V | 0.9004 | likely_pathogenic | 0.9023 | pathogenic | -0.907 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | I |
| P/W | 0.9995 | likely_pathogenic | 0.9994 | pathogenic | -1.417 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | I |
| P/Y | 0.9983 | likely_pathogenic | 0.9981 | pathogenic | -1.143 | Destabilizing | 1.0 | D | 0.8 | deleterious | 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.