Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26210 | 78853;78854;78855 | chr2:178567504;178567503;178567502 | chr2:179432231;179432230;179432229 |
| N2AB | 24569 | 73930;73931;73932 | chr2:178567504;178567503;178567502 | chr2:179432231;179432230;179432229 |
| N2A | 23642 | 71149;71150;71151 | chr2:178567504;178567503;178567502 | chr2:179432231;179432230;179432229 |
| N2B | 17145 | 51658;51659;51660 | chr2:178567504;178567503;178567502 | chr2:179432231;179432230;179432229 |
| Novex-1 | 17270 | 52033;52034;52035 | chr2:178567504;178567503;178567502 | chr2:179432231;179432230;179432229 |
| Novex-2 | 17337 | 52234;52235;52236 | chr2:178567504;178567503;178567502 | chr2:179432231;179432230;179432229 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | None | None | 0.989 | N | 0.749 | 0.41 | 0.405560941015 | gnomAD-4.0.0 | 6.84563E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99705E-07 | 0 | 0 |
| T/K | rs879021950  |
-0.387 | 0.957 | N | 0.677 | 0.33 | None | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 1.14758E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/K | rs879021950 |
-0.387 | 0.957 | N | 0.677 | 0.33 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/K | rs879021950 |
-0.387 | 0.957 | N | 0.677 | 0.33 | None | gnomAD-4.0.0 | 2.48003E-06 | None | None | None | None | I | None | 5.34217E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1009 | likely_benign | 0.1031 | benign | -0.968 | Destabilizing | 0.726 | D | 0.488 | neutral | N | 0.456719299 | None | None | I |
| T/C | 0.455 | ambiguous | 0.4184 | ambiguous | -0.53 | Destabilizing | 0.999 | D | 0.743 | deleterious | None | None | None | None | I |
| T/D | 0.4433 | ambiguous | 0.4701 | ambiguous | -0.069 | Destabilizing | 0.983 | D | 0.675 | neutral | None | None | None | None | I |
| T/E | 0.4601 | ambiguous | 0.5035 | ambiguous | -0.001 | Destabilizing | 0.983 | D | 0.673 | neutral | None | None | None | None | I |
| T/F | 0.4113 | ambiguous | 0.423 | ambiguous | -0.893 | Destabilizing | 0.992 | D | 0.8 | deleterious | None | None | None | None | I |
| T/G | 0.3237 | likely_benign | 0.3165 | benign | -1.286 | Destabilizing | 0.895 | D | 0.61 | neutral | None | None | None | None | I |
| T/H | 0.4121 | ambiguous | 0.4159 | ambiguous | -1.388 | Destabilizing | 0.998 | D | 0.774 | deleterious | None | None | None | None | I |
| T/I | 0.1978 | likely_benign | 0.2007 | benign | -0.188 | Destabilizing | 0.989 | D | 0.749 | deleterious | N | 0.491966757 | None | None | I |
| T/K | 0.4222 | ambiguous | 0.4626 | ambiguous | -0.539 | Destabilizing | 0.957 | D | 0.677 | prob.neutral | N | 0.513544624 | None | None | I |
| T/L | 0.1566 | likely_benign | 0.1603 | benign | -0.188 | Destabilizing | 0.944 | D | 0.599 | neutral | None | None | None | None | I |
| T/M | 0.1072 | likely_benign | 0.1043 | benign | -0.049 | Destabilizing | 0.999 | D | 0.758 | deleterious | None | None | None | None | I |
| T/N | 0.1286 | likely_benign | 0.1279 | benign | -0.692 | Destabilizing | 0.968 | D | 0.695 | prob.neutral | None | None | None | None | I |
| T/P | 0.139 | likely_benign | 0.1444 | benign | -0.415 | Destabilizing | 0.989 | D | 0.747 | deleterious | N | 0.50332763 | None | None | I |
| T/Q | 0.3776 | ambiguous | 0.4007 | ambiguous | -0.696 | Destabilizing | 0.983 | D | 0.761 | deleterious | None | None | None | None | I |
| T/R | 0.3797 | ambiguous | 0.4348 | ambiguous | -0.438 | Destabilizing | 0.978 | D | 0.744 | deleterious | N | 0.461238749 | None | None | I |
| T/S | 0.1175 | likely_benign | 0.1162 | benign | -1.051 | Destabilizing | 0.146 | N | 0.309 | neutral | N | 0.451127941 | None | None | I |
| T/V | 0.149 | likely_benign | 0.1479 | benign | -0.415 | Destabilizing | 0.944 | D | 0.567 | neutral | None | None | None | None | I |
| T/W | 0.7897 | likely_pathogenic | 0.7973 | pathogenic | -0.85 | Destabilizing | 0.999 | D | 0.78 | deleterious | None | None | None | None | I |
| T/Y | 0.4082 | ambiguous | 0.4248 | ambiguous | -0.586 | Destabilizing | 0.997 | D | 0.799 | deleterious | None | None | None | None | I |
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.