Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22414 | 67465;67466;67467 | chr2:178580047;178580046;178580045 | chr2:179444774;179444773;179444772 |
| N2AB | 20773 | 62542;62543;62544 | chr2:178580047;178580046;178580045 | chr2:179444774;179444773;179444772 |
| N2A | 19846 | 59761;59762;59763 | chr2:178580047;178580046;178580045 | chr2:179444774;179444773;179444772 |
| N2B | 13349 | 40270;40271;40272 | chr2:178580047;178580046;178580045 | chr2:179444774;179444773;179444772 |
| Novex-1 | 13474 | 40645;40646;40647 | chr2:178580047;178580046;178580045 | chr2:179444774;179444773;179444772 |
| Novex-2 | 13541 | 40846;40847;40848 | chr2:178580047;178580046;178580045 | chr2:179444774;179444773;179444772 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/S | rs761987832  |
-1.198 | 0.892 | N | 0.684 | 0.233 | 0.252681307341 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| R/S | rs761987832 |
-1.198 | 0.892 | N | 0.684 | 0.233 | 0.252681307341 | 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 |
| R/S | rs761987832 |
-1.198 | 0.892 | N | 0.684 | 0.233 | 0.252681307341 | gnomAD-4.0.0 | 1.36877E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79936E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6338 | likely_pathogenic | 0.5 | ambiguous | -1.204 | Destabilizing | 0.845 | D | 0.625 | neutral | None | None | None | None | N |
| R/C | 0.2639 | likely_benign | 0.1895 | benign | -1.114 | Destabilizing | 0.999 | D | 0.745 | deleterious | None | None | None | None | N |
| R/D | 0.9031 | likely_pathogenic | 0.8217 | pathogenic | -0.088 | Destabilizing | 0.975 | D | 0.739 | prob.delet. | None | None | None | None | N |
| R/E | 0.6655 | likely_pathogenic | 0.5199 | ambiguous | 0.091 | Stabilizing | 0.845 | D | 0.541 | neutral | None | None | None | None | N |
| R/F | 0.7311 | likely_pathogenic | 0.6098 | pathogenic | -0.753 | Destabilizing | 0.996 | D | 0.753 | deleterious | None | None | None | None | N |
| R/G | 0.6383 | likely_pathogenic | 0.4929 | ambiguous | -1.548 | Destabilizing | 0.892 | D | 0.667 | neutral | N | 0.475078541 | None | None | N |
| R/H | 0.1438 | likely_benign | 0.1105 | benign | -1.638 | Destabilizing | 0.987 | D | 0.629 | neutral | None | None | None | None | N |
| R/I | 0.3911 | ambiguous | 0.2959 | benign | -0.249 | Destabilizing | 0.983 | D | 0.761 | deleterious | N | 0.512803623 | None | None | N |
| R/K | 0.1317 | likely_benign | 0.102 | benign | -0.842 | Destabilizing | 0.025 | N | 0.255 | neutral | N | 0.404444007 | None | None | N |
| R/L | 0.3508 | ambiguous | 0.2709 | benign | -0.249 | Destabilizing | 0.916 | D | 0.667 | neutral | None | None | None | None | N |
| R/M | 0.4359 | ambiguous | 0.3272 | benign | -0.711 | Destabilizing | 0.999 | D | 0.722 | prob.delet. | None | None | None | None | N |
| R/N | 0.8084 | likely_pathogenic | 0.6902 | pathogenic | -0.595 | Destabilizing | 0.975 | D | 0.611 | neutral | None | None | None | None | N |
| R/P | 0.7245 | likely_pathogenic | 0.6003 | pathogenic | -0.549 | Destabilizing | 0.987 | D | 0.762 | deleterious | None | None | None | None | N |
| R/Q | 0.1791 | likely_benign | 0.1335 | benign | -0.63 | Destabilizing | 0.975 | D | 0.605 | neutral | None | None | None | None | N |
| R/S | 0.7445 | likely_pathogenic | 0.613 | pathogenic | -1.479 | Destabilizing | 0.892 | D | 0.684 | prob.neutral | N | 0.506069652 | None | None | N |
| R/T | 0.4004 | ambiguous | 0.2892 | benign | -1.088 | Destabilizing | 0.967 | D | 0.729 | prob.delet. | N | 0.426968576 | None | None | N |
| R/V | 0.4781 | ambiguous | 0.3672 | ambiguous | -0.549 | Destabilizing | 0.975 | D | 0.756 | deleterious | None | None | None | None | N |
| R/W | 0.3077 | likely_benign | 0.242 | benign | -0.319 | Destabilizing | 0.999 | D | 0.725 | prob.delet. | None | None | None | None | N |
| R/Y | 0.5659 | likely_pathogenic | 0.45 | ambiguous | -0.116 | Destabilizing | 0.996 | D | 0.765 | 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.