Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19912 | 59959;59960;59961 | chr2:178592170;178592169;178592168 | chr2:179456897;179456896;179456895 |
| N2AB | 18271 | 55036;55037;55038 | chr2:178592170;178592169;178592168 | chr2:179456897;179456896;179456895 |
| N2A | 17344 | 52255;52256;52257 | chr2:178592170;178592169;178592168 | chr2:179456897;179456896;179456895 |
| N2B | 10847 | 32764;32765;32766 | chr2:178592170;178592169;178592168 | chr2:179456897;179456896;179456895 |
| Novex-1 | 10972 | 33139;33140;33141 | chr2:178592170;178592169;178592168 | chr2:179456897;179456896;179456895 |
| Novex-2 | 11039 | 33340;33341;33342 | chr2:178592170;178592169;178592168 | chr2:179456897;179456896;179456895 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs1251975601  |
-2.301 | 1.0 | D | 0.849 | 0.764 | 0.838724148165 | gnomAD-2.1.1 | 8.1E-06 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| Y/C | rs1251975601 |
-2.301 | 1.0 | D | 0.849 | 0.764 | 0.838724148165 | 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 |
| Y/C | rs1251975601 |
-2.301 | 1.0 | D | 0.849 | 0.764 | 0.838724148165 | gnomAD-4.0.0 | 4.34053E-06 | None | None | None | None | N | None | 0 | 1.66978E-05 | None | 0 | 0 | None | 0 | 1.64636E-04 | 2.54357E-06 | 0 | 3.20533E-05 |
| Y/S | None | None | 0.998 | D | 0.805 | 0.767 | 0.889296670409 | gnomAD-4.0.0 | 6.84612E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99696E-07 | 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 | 0.9955 | likely_pathogenic | 0.9943 | pathogenic | -3.349 | Highly Destabilizing | 0.985 | D | 0.807 | deleterious | None | None | None | None | N |
| Y/C | 0.9188 | likely_pathogenic | 0.9001 | pathogenic | -1.998 | Destabilizing | 1.0 | D | 0.849 | deleterious | D | 0.640029285 | None | None | N |
| Y/D | 0.9938 | likely_pathogenic | 0.9936 | pathogenic | -3.768 | Highly Destabilizing | 0.998 | D | 0.892 | deleterious | D | 0.640432894 | None | None | N |
| Y/E | 0.9987 | likely_pathogenic | 0.9986 | pathogenic | -3.552 | Highly Destabilizing | 0.999 | D | 0.845 | deleterious | None | None | None | None | N |
| Y/F | 0.1679 | likely_benign | 0.1439 | benign | -1.28 | Destabilizing | 0.031 | N | 0.335 | neutral | D | 0.566158001 | None | None | N |
| Y/G | 0.9916 | likely_pathogenic | 0.9912 | pathogenic | -3.766 | Highly Destabilizing | 0.999 | D | 0.829 | deleterious | None | None | None | None | N |
| Y/H | 0.9439 | likely_pathogenic | 0.9431 | pathogenic | -2.508 | Highly Destabilizing | 0.998 | D | 0.682 | prob.neutral | D | 0.624009924 | None | None | N |
| Y/I | 0.9584 | likely_pathogenic | 0.9506 | pathogenic | -1.943 | Destabilizing | 0.97 | D | 0.767 | deleterious | None | None | None | None | N |
| Y/K | 0.9982 | likely_pathogenic | 0.9981 | pathogenic | -2.327 | Highly Destabilizing | 0.999 | D | 0.845 | deleterious | None | None | None | None | N |
| Y/L | 0.9421 | likely_pathogenic | 0.9335 | pathogenic | -1.943 | Destabilizing | 0.871 | D | 0.726 | prob.delet. | None | None | None | None | N |
| Y/M | 0.9781 | likely_pathogenic | 0.975 | pathogenic | -1.763 | Destabilizing | 0.999 | D | 0.783 | deleterious | None | None | None | None | N |
| Y/N | 0.9715 | likely_pathogenic | 0.9735 | pathogenic | -3.139 | Highly Destabilizing | 0.998 | D | 0.862 | deleterious | D | 0.640432894 | None | None | N |
| Y/P | 0.9993 | likely_pathogenic | 0.9991 | pathogenic | -2.43 | Highly Destabilizing | 0.999 | D | 0.89 | deleterious | None | None | None | None | N |
| Y/Q | 0.9973 | likely_pathogenic | 0.9972 | pathogenic | -2.873 | Highly Destabilizing | 0.999 | D | 0.769 | deleterious | None | None | None | None | N |
| Y/R | 0.9928 | likely_pathogenic | 0.9924 | pathogenic | -2.111 | Highly Destabilizing | 0.999 | D | 0.861 | deleterious | None | None | None | None | N |
| Y/S | 0.9839 | likely_pathogenic | 0.9826 | pathogenic | -3.458 | Highly Destabilizing | 0.998 | D | 0.805 | deleterious | D | 0.640432894 | None | None | N |
| Y/T | 0.9913 | likely_pathogenic | 0.9904 | pathogenic | -3.116 | Highly Destabilizing | 0.999 | D | 0.811 | deleterious | None | None | None | None | N |
| Y/V | 0.9355 | likely_pathogenic | 0.9216 | pathogenic | -2.43 | Highly Destabilizing | 0.97 | D | 0.745 | deleterious | None | None | None | None | N |
| Y/W | 0.7928 | likely_pathogenic | 0.7791 | pathogenic | -0.554 | Destabilizing | 0.999 | D | 0.694 | prob.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.