Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1029 | 3310;3311;3312 | chr2:178782821;178782820;178782819 | chr2:179647548;179647547;179647546 |
| N2AB | 1029 | 3310;3311;3312 | chr2:178782821;178782820;178782819 | chr2:179647548;179647547;179647546 |
| N2A | 1029 | 3310;3311;3312 | chr2:178782821;178782820;178782819 | chr2:179647548;179647547;179647546 |
| N2B | 983 | 3172;3173;3174 | chr2:178782821;178782820;178782819 | chr2:179647548;179647547;179647546 |
| Novex-1 | 983 | 3172;3173;3174 | chr2:178782821;178782820;178782819 | chr2:179647548;179647547;179647546 |
| Novex-2 | 983 | 3172;3173;3174 | chr2:178782821;178782820;178782819 | chr2:179647548;179647547;179647546 |
| Novex-3 | 1029 | 3310;3311;3312 | chr2:178782821;178782820;178782819 | chr2:179647548;179647547;179647546 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs774126306  |
-0.302 | 0.999 | N | 0.738 | 0.535 | None | gnomAD-2.1.1 | 1.42E-05 | None | None | None | None | N | None | 1.20163E-04 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| Y/C | rs774126306 |
-0.302 | 0.999 | N | 0.738 | 0.535 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/C | rs774126306 |
-0.302 | 0.999 | N | 0.738 | 0.535 | None | gnomAD-4.0.0 | 6.81985E-06 | None | None | None | None | N | None | 9.34554E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69512E-06 | 2.19703E-05 | 0 |
| Y/S | rs774126306 |
-1.214 | 0.982 | N | 0.717 | 0.48 | 0.681924071509 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.45E-05 | None | 0 | None | 0 | 0 | 0 |
| Y/S | rs774126306 |
-1.214 | 0.982 | N | 0.717 | 0.48 | 0.681924071509 | gnomAD-4.0.0 | 6.84583E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52054E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9362 | likely_pathogenic | 0.9409 | pathogenic | -1.566 | Destabilizing | 0.953 | D | 0.685 | prob.neutral | None | None | None | None | N |
| Y/C | 0.7499 | likely_pathogenic | 0.5955 | pathogenic | -0.321 | Destabilizing | 0.999 | D | 0.738 | prob.delet. | N | 0.497287217 | None | None | N |
| Y/D | 0.8809 | likely_pathogenic | 0.8938 | pathogenic | 0.488 | Stabilizing | 0.982 | D | 0.759 | deleterious | N | 0.477694258 | None | None | N |
| Y/E | 0.9658 | likely_pathogenic | 0.9682 | pathogenic | 0.52 | Stabilizing | 0.986 | D | 0.696 | prob.neutral | None | None | None | None | N |
| Y/F | 0.1641 | likely_benign | 0.165 | benign | -0.709 | Destabilizing | 0.969 | D | 0.561 | neutral | N | 0.469121623 | None | None | N |
| Y/G | 0.955 | likely_pathogenic | 0.9579 | pathogenic | -1.825 | Destabilizing | 0.986 | D | 0.706 | prob.neutral | None | None | None | None | N |
| Y/H | 0.5773 | likely_pathogenic | 0.5988 | pathogenic | -0.325 | Destabilizing | 0.1 | N | 0.295 | neutral | N | 0.446527736 | None | None | N |
| Y/I | 0.876 | likely_pathogenic | 0.8802 | pathogenic | -0.838 | Destabilizing | 0.993 | D | 0.772 | deleterious | None | None | None | None | N |
| Y/K | 0.9728 | likely_pathogenic | 0.9735 | pathogenic | -0.353 | Destabilizing | 0.986 | D | 0.751 | deleterious | None | None | None | None | N |
| Y/L | 0.7854 | likely_pathogenic | 0.7951 | pathogenic | -0.838 | Destabilizing | 0.953 | D | 0.696 | prob.neutral | None | None | None | None | N |
| Y/M | 0.9188 | likely_pathogenic | 0.9192 | pathogenic | -0.496 | Destabilizing | 0.999 | D | 0.725 | prob.delet. | None | None | None | None | N |
| Y/N | 0.6921 | likely_pathogenic | 0.6977 | pathogenic | -0.52 | Destabilizing | 0.982 | D | 0.761 | deleterious | N | 0.432242351 | None | None | N |
| Y/P | 0.9886 | likely_pathogenic | 0.9885 | pathogenic | -1.067 | Destabilizing | 0.998 | D | 0.766 | deleterious | None | None | None | None | N |
| Y/Q | 0.9425 | likely_pathogenic | 0.9463 | pathogenic | -0.492 | Destabilizing | 0.986 | D | 0.764 | deleterious | None | None | None | None | N |
| Y/R | 0.9162 | likely_pathogenic | 0.9189 | pathogenic | 0.066 | Stabilizing | 0.986 | D | 0.757 | deleterious | None | None | None | None | N |
| Y/S | 0.6949 | likely_pathogenic | 0.7097 | pathogenic | -1.122 | Destabilizing | 0.982 | D | 0.717 | prob.delet. | N | 0.419208406 | None | None | N |
| Y/T | 0.8864 | likely_pathogenic | 0.8949 | pathogenic | -0.999 | Destabilizing | 0.993 | D | 0.757 | deleterious | None | None | None | None | N |
| Y/V | 0.8063 | likely_pathogenic | 0.8122 | pathogenic | -1.067 | Destabilizing | 0.993 | D | 0.721 | prob.delet. | None | None | None | None | N |
| Y/W | 0.6998 | likely_pathogenic | 0.7178 | pathogenic | -0.501 | Destabilizing | 0.999 | D | 0.657 | 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.