Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23471 | 70636;70637;70638 | chr2:178575721;178575720;178575719 | chr2:179440448;179440447;179440446 |
| N2AB | 21830 | 65713;65714;65715 | chr2:178575721;178575720;178575719 | chr2:179440448;179440447;179440446 |
| N2A | 20903 | 62932;62933;62934 | chr2:178575721;178575720;178575719 | chr2:179440448;179440447;179440446 |
| N2B | 14406 | 43441;43442;43443 | chr2:178575721;178575720;178575719 | chr2:179440448;179440447;179440446 |
| Novex-1 | 14531 | 43816;43817;43818 | chr2:178575721;178575720;178575719 | chr2:179440448;179440447;179440446 |
| Novex-2 | 14598 | 44017;44018;44019 | chr2:178575721;178575720;178575719 | chr2:179440448;179440447;179440446 |
| 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/M | rs764793576  |
-1.382 | 0.99 | N | 0.703 | 0.339 | 0.550334908387 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| I/T | rs1475765674 |
None | 0.972 | N | 0.663 | 0.414 | 0.70371367467 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs1475765674 |
None | 0.972 | N | 0.663 | 0.414 | 0.70371367467 | gnomAD-4.0.0 | 4.33881E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.934E-06 | 0 | 0 |
| I/V | None | None | 0.006 | N | 0.281 | 0.06 | 0.470890129789 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31251E-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 | 0.816 | likely_pathogenic | 0.8407 | pathogenic | -2.469 | Highly Destabilizing | 0.987 | D | 0.633 | neutral | None | None | None | None | N |
| I/C | 0.916 | likely_pathogenic | 0.9163 | pathogenic | -1.856 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| I/D | 0.9928 | likely_pathogenic | 0.9939 | pathogenic | -3.029 | Highly Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| I/E | 0.9693 | likely_pathogenic | 0.973 | pathogenic | -2.916 | Highly Destabilizing | 0.999 | D | 0.735 | prob.delet. | None | None | None | None | N |
| I/F | 0.5503 | ambiguous | 0.5824 | pathogenic | -1.581 | Destabilizing | 0.994 | D | 0.705 | prob.neutral | N | 0.47834377 | None | None | N |
| I/G | 0.9843 | likely_pathogenic | 0.9869 | pathogenic | -2.903 | Highly Destabilizing | 0.999 | D | 0.736 | prob.delet. | None | None | None | None | N |
| I/H | 0.9011 | likely_pathogenic | 0.9005 | pathogenic | -2.21 | Highly Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| I/K | 0.8806 | likely_pathogenic | 0.8931 | pathogenic | -1.887 | Destabilizing | 0.969 | D | 0.734 | prob.delet. | None | None | None | None | N |
| I/L | 0.3303 | likely_benign | 0.3561 | ambiguous | -1.253 | Destabilizing | 0.232 | N | 0.485 | neutral | N | 0.491177557 | None | None | N |
| I/M | 0.3167 | likely_benign | 0.3454 | ambiguous | -1.144 | Destabilizing | 0.99 | D | 0.703 | prob.neutral | N | 0.501323097 | None | None | N |
| I/N | 0.9163 | likely_pathogenic | 0.9213 | pathogenic | -2.026 | Highly Destabilizing | 1.0 | D | 0.787 | deleterious | N | 0.47920269 | None | None | N |
| I/P | 0.9971 | likely_pathogenic | 0.9976 | pathogenic | -1.637 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| I/Q | 0.9259 | likely_pathogenic | 0.9272 | pathogenic | -2.093 | Highly Destabilizing | 0.999 | D | 0.779 | deleterious | None | None | None | None | N |
| I/R | 0.7951 | likely_pathogenic | 0.8046 | pathogenic | -1.344 | Destabilizing | 0.998 | D | 0.783 | deleterious | None | None | None | None | N |
| I/S | 0.8537 | likely_pathogenic | 0.8645 | pathogenic | -2.613 | Highly Destabilizing | 0.999 | D | 0.659 | neutral | N | 0.477276906 | None | None | N |
| I/T | 0.4548 | ambiguous | 0.4876 | ambiguous | -2.383 | Highly Destabilizing | 0.972 | D | 0.663 | neutral | N | 0.520190955 | None | None | N |
| I/V | 0.0823 | likely_benign | 0.0863 | benign | -1.637 | Destabilizing | 0.006 | N | 0.281 | neutral | N | 0.47132236 | None | None | N |
| I/W | 0.9602 | likely_pathogenic | 0.9622 | pathogenic | -1.896 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| I/Y | 0.8934 | likely_pathogenic | 0.9 | pathogenic | -1.676 | Destabilizing | 0.98 | D | 0.71 | prob.delet. | 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.