Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14803 | 44632;44633;44634 | chr2:178629318;178629317;178629316 | chr2:179494045;179494044;179494043 |
| N2AB | 13162 | 39709;39710;39711 | chr2:178629318;178629317;178629316 | chr2:179494045;179494044;179494043 |
| N2A | 12235 | 36928;36929;36930 | chr2:178629318;178629317;178629316 | chr2:179494045;179494044;179494043 |
| N2B | 5738 | 17437;17438;17439 | chr2:178629318;178629317;178629316 | chr2:179494045;179494044;179494043 |
| Novex-1 | 5863 | 17812;17813;17814 | chr2:178629318;178629317;178629316 | chr2:179494045;179494044;179494043 |
| Novex-2 | 5930 | 18013;18014;18015 | chr2:178629318;178629317;178629316 | chr2:179494045;179494044;179494043 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/P | None | None | 1.0 | D | 0.818 | 0.763 | 0.908283339285 | gnomAD-4.0.0 | 1.59389E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86285E-06 | 0 | 0 |
| L/Q | rs1332557578  |
-1.963 | 1.0 | D | 0.814 | 0.757 | 0.884855417834 | 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 |
| L/Q | rs1332557578 |
-1.963 | 1.0 | D | 0.814 | 0.757 | 0.884855417834 | gnomAD-4.0.0 | 1.59389E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86285E-06 | 0 | 0 |
| L/V | rs757335885 |
-1.085 | 0.999 | D | 0.479 | 0.381 | 0.609419018514 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.13033E-04 | None | 0 | None | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.6056 | likely_pathogenic | 0.5877 | pathogenic | -2.299 | Highly Destabilizing | 0.999 | D | 0.667 | neutral | None | None | None | None | N |
| L/C | 0.7764 | likely_pathogenic | 0.7788 | pathogenic | -1.396 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| L/D | 0.9842 | likely_pathogenic | 0.986 | pathogenic | -2.786 | Highly Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| L/E | 0.8644 | likely_pathogenic | 0.8741 | pathogenic | -2.545 | Highly Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| L/F | 0.3858 | ambiguous | 0.4365 | ambiguous | -1.433 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| L/G | 0.9123 | likely_pathogenic | 0.9109 | pathogenic | -2.817 | Highly Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| L/H | 0.7937 | likely_pathogenic | 0.8274 | pathogenic | -2.258 | Highly Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| L/I | 0.1183 | likely_benign | 0.1222 | benign | -0.796 | Destabilizing | 0.999 | D | 0.469 | neutral | N | 0.499867236 | None | None | N |
| L/K | 0.805 | likely_pathogenic | 0.8269 | pathogenic | -1.871 | Destabilizing | 1.0 | D | 0.82 | deleterious | None | None | None | None | N |
| L/M | 0.1468 | likely_benign | 0.1542 | benign | -0.624 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| L/N | 0.9348 | likely_pathogenic | 0.9389 | pathogenic | -2.296 | Highly Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| L/P | 0.9333 | likely_pathogenic | 0.9251 | pathogenic | -1.28 | Destabilizing | 1.0 | D | 0.818 | deleterious | D | 0.68373273 | None | None | N |
| L/Q | 0.631 | likely_pathogenic | 0.642 | pathogenic | -2.139 | Highly Destabilizing | 1.0 | D | 0.814 | deleterious | D | 0.722591608 | None | None | N |
| L/R | 0.7209 | likely_pathogenic | 0.7466 | pathogenic | -1.632 | Destabilizing | 1.0 | D | 0.829 | deleterious | D | 0.722174477 | None | None | N |
| L/S | 0.8538 | likely_pathogenic | 0.8559 | pathogenic | -2.903 | Highly Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| L/T | 0.582 | likely_pathogenic | 0.5768 | pathogenic | -2.519 | Highly Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | N |
| L/V | 0.127 | likely_benign | 0.1311 | benign | -1.28 | Destabilizing | 0.999 | D | 0.479 | neutral | D | 0.522287714 | None | None | N |
| L/W | 0.5849 | likely_pathogenic | 0.6254 | pathogenic | -1.843 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| L/Y | 0.7438 | likely_pathogenic | 0.7789 | pathogenic | -1.495 | Destabilizing | 1.0 | D | 0.819 | 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.