Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16832 | 50719;50720;50721 | chr2:178611815;178611814;178611813 | chr2:179476542;179476541;179476540 |
| N2AB | 15191 | 45796;45797;45798 | chr2:178611815;178611814;178611813 | chr2:179476542;179476541;179476540 |
| N2A | 14264 | 43015;43016;43017 | chr2:178611815;178611814;178611813 | chr2:179476542;179476541;179476540 |
| N2B | 7767 | 23524;23525;23526 | chr2:178611815;178611814;178611813 | chr2:179476542;179476541;179476540 |
| Novex-1 | 7892 | 23899;23900;23901 | chr2:178611815;178611814;178611813 | chr2:179476542;179476541;179476540 |
| Novex-2 | 7959 | 24100;24101;24102 | chr2:178611815;178611814;178611813 | chr2:179476542;179476541;179476540 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs1465354124  |
-0.476 | 0.946 | D | 0.781 | 0.393 | 0.303453137403 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| A/T | rs1465354124 |
-0.476 | 0.946 | D | 0.781 | 0.393 | 0.303453137403 | gnomAD-4.0.0 | 1.59316E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86161E-06 | 0 | 0 |
| A/V | None | None | 0.464 | N | 0.526 | 0.198 | 0.252162846088 | gnomAD-4.0.0 | 1.59318E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86169E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7696 | likely_pathogenic | 0.8088 | pathogenic | -0.821 | Destabilizing | 0.998 | D | 0.818 | deleterious | None | None | None | None | I |
| A/D | 0.8765 | likely_pathogenic | 0.9562 | pathogenic | -0.681 | Destabilizing | 0.973 | D | 0.821 | deleterious | D | 0.585648467 | None | None | I |
| A/E | 0.8518 | likely_pathogenic | 0.9238 | pathogenic | -0.847 | Destabilizing | 0.979 | D | 0.787 | deleterious | None | None | None | None | I |
| A/F | 0.7128 | likely_pathogenic | 0.8215 | pathogenic | -0.96 | Destabilizing | 0.959 | D | 0.835 | deleterious | None | None | None | None | I |
| A/G | 0.4413 | ambiguous | 0.6076 | pathogenic | -0.287 | Destabilizing | 0.911 | D | 0.633 | neutral | D | 0.563366916 | None | None | I |
| A/H | 0.8761 | likely_pathogenic | 0.9383 | pathogenic | -0.259 | Destabilizing | 0.998 | D | 0.845 | deleterious | None | None | None | None | I |
| A/I | 0.7272 | likely_pathogenic | 0.8005 | pathogenic | -0.431 | Destabilizing | 0.046 | N | 0.485 | neutral | None | None | None | None | I |
| A/K | 0.9458 | likely_pathogenic | 0.9749 | pathogenic | -0.624 | Destabilizing | 0.979 | D | 0.791 | deleterious | None | None | None | None | I |
| A/L | 0.5526 | ambiguous | 0.6714 | pathogenic | -0.431 | Destabilizing | 0.535 | D | 0.513 | neutral | None | None | None | None | I |
| A/M | 0.6531 | likely_pathogenic | 0.7629 | pathogenic | -0.461 | Destabilizing | 0.989 | D | 0.821 | deleterious | None | None | None | None | I |
| A/N | 0.7403 | likely_pathogenic | 0.8708 | pathogenic | -0.332 | Destabilizing | 0.993 | D | 0.837 | deleterious | None | None | None | None | I |
| A/P | 0.9426 | likely_pathogenic | 0.977 | pathogenic | -0.349 | Destabilizing | 0.991 | D | 0.805 | deleterious | D | 0.680798471 | None | None | I |
| A/Q | 0.8233 | likely_pathogenic | 0.9103 | pathogenic | -0.651 | Destabilizing | 0.993 | D | 0.819 | deleterious | None | None | None | None | I |
| A/R | 0.8784 | likely_pathogenic | 0.9309 | pathogenic | -0.1 | Destabilizing | 0.979 | D | 0.817 | deleterious | None | None | None | None | I |
| A/S | 0.2433 | likely_benign | 0.3441 | ambiguous | -0.49 | Destabilizing | 0.911 | D | 0.616 | neutral | D | 0.529236017 | None | None | I |
| A/T | 0.4549 | ambiguous | 0.6251 | pathogenic | -0.586 | Destabilizing | 0.946 | D | 0.781 | deleterious | D | 0.600150284 | None | None | I |
| A/V | 0.4552 | ambiguous | 0.5461 | ambiguous | -0.349 | Destabilizing | 0.464 | N | 0.526 | neutral | N | 0.479860492 | None | None | I |
| A/W | 0.9514 | likely_pathogenic | 0.9766 | pathogenic | -1.058 | Destabilizing | 0.998 | D | 0.85 | deleterious | None | None | None | None | I |
| A/Y | 0.8414 | likely_pathogenic | 0.9059 | pathogenic | -0.732 | Destabilizing | 0.979 | D | 0.848 | 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.