Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16553 | 49882;49883;49884 | chr2:178613064;178613063;178613062 | chr2:179477791;179477790;179477789 |
| N2AB | 14912 | 44959;44960;44961 | chr2:178613064;178613063;178613062 | chr2:179477791;179477790;179477789 |
| N2A | 13985 | 42178;42179;42180 | chr2:178613064;178613063;178613062 | chr2:179477791;179477790;179477789 |
| N2B | 7488 | 22687;22688;22689 | chr2:178613064;178613063;178613062 | chr2:179477791;179477790;179477789 |
| Novex-1 | 7613 | 23062;23063;23064 | chr2:178613064;178613063;178613062 | chr2:179477791;179477790;179477789 |
| Novex-2 | 7680 | 23263;23264;23265 | chr2:178613064;178613063;178613062 | chr2:179477791;179477790;179477789 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/C | None | None | 1.0 | N | 0.725 | 0.335 | 0.390842690916 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| W/R | rs1334958583  |
None | 1.0 | N | 0.751 | 0.421 | 0.435371449458 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| W/R | rs1334958583 |
None | 1.0 | N | 0.751 | 0.421 | 0.435371449458 | gnomAD-4.0.0 | 6.57851E-06 | None | None | None | None | N | None | 0 | 6.56168E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/A | 0.7363 | likely_pathogenic | 0.7482 | pathogenic | -1.763 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| W/C | 0.9179 | likely_pathogenic | 0.9228 | pathogenic | -0.222 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | N | 0.468675807 | None | None | N |
| W/D | 0.9364 | likely_pathogenic | 0.9476 | pathogenic | -0.195 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| W/E | 0.9545 | likely_pathogenic | 0.9646 | pathogenic | -0.15 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| W/F | 0.3915 | ambiguous | 0.3874 | ambiguous | -1.106 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | N |
| W/G | 0.43 | ambiguous | 0.4457 | ambiguous | -1.951 | Destabilizing | 1.0 | D | 0.636 | neutral | N | 0.454907728 | None | None | N |
| W/H | 0.878 | likely_pathogenic | 0.8847 | pathogenic | -0.708 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| W/I | 0.9334 | likely_pathogenic | 0.9428 | pathogenic | -1.148 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | N |
| W/K | 0.9768 | likely_pathogenic | 0.9829 | pathogenic | -0.466 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| W/L | 0.6952 | likely_pathogenic | 0.7354 | pathogenic | -1.148 | Destabilizing | 1.0 | D | 0.636 | neutral | N | 0.467085622 | None | None | N |
| W/M | 0.8961 | likely_pathogenic | 0.9043 | pathogenic | -0.748 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| W/N | 0.9249 | likely_pathogenic | 0.9341 | pathogenic | -0.661 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| W/P | 0.9826 | likely_pathogenic | 0.9874 | pathogenic | -1.357 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | N |
| W/Q | 0.9531 | likely_pathogenic | 0.9585 | pathogenic | -0.605 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| W/R | 0.9571 | likely_pathogenic | 0.9694 | pathogenic | -0.195 | Destabilizing | 1.0 | D | 0.751 | deleterious | N | 0.466045397 | None | None | N |
| W/S | 0.491 | ambiguous | 0.5025 | ambiguous | -1.051 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | N | 0.418996491 | None | None | N |
| W/T | 0.8663 | likely_pathogenic | 0.8774 | pathogenic | -0.95 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| W/V | 0.886 | likely_pathogenic | 0.9037 | pathogenic | -1.357 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| W/Y | 0.6053 | likely_pathogenic | 0.5949 | pathogenic | -1.135 | Destabilizing | 1.0 | D | 0.649 | neutral | 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.