Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18612 | 56059;56060;56061 | chr2:178601070;178601069;178601068 | chr2:179465797;179465796;179465795 |
| N2AB | 16971 | 51136;51137;51138 | chr2:178601070;178601069;178601068 | chr2:179465797;179465796;179465795 |
| N2A | 16044 | 48355;48356;48357 | chr2:178601070;178601069;178601068 | chr2:179465797;179465796;179465795 |
| N2B | 9547 | 28864;28865;28866 | chr2:178601070;178601069;178601068 | chr2:179465797;179465796;179465795 |
| Novex-1 | 9672 | 29239;29240;29241 | chr2:178601070;178601069;178601068 | chr2:179465797;179465796;179465795 |
| Novex-2 | 9739 | 29440;29441;29442 | chr2:178601070;178601069;178601068 | chr2:179465797;179465796;179465795 |
| 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 | 0.999 | N | 0.754 | 0.429 | 0.520803792171 | gnomAD-4.0.0 | 1.37032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80063E-06 | 0 | 0 |
| T/N | rs765352575  |
-1.006 | 0.997 | N | 0.623 | 0.381 | 0.47290127212 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.3E-05 | None | 0 | 0 | 0 |
| T/N | rs765352575 |
-1.006 | 0.997 | N | 0.623 | 0.381 | 0.47290127212 | gnomAD-4.0.0 | 1.37032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16347E-05 | 1.65893E-05 |
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 | 0.1845 | likely_benign | 0.1794 | benign | -0.78 | Destabilizing | 0.978 | D | 0.489 | neutral | N | 0.492768403 | None | None | N |
| T/C | 0.6302 | likely_pathogenic | 0.6495 | pathogenic | -0.394 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| T/D | 0.5805 | likely_pathogenic | 0.6089 | pathogenic | -0.777 | Destabilizing | 0.998 | D | 0.668 | neutral | None | None | None | None | N |
| T/E | 0.4711 | ambiguous | 0.4758 | ambiguous | -0.747 | Destabilizing | 0.983 | D | 0.615 | neutral | None | None | None | None | N |
| T/F | 0.4764 | ambiguous | 0.4655 | ambiguous | -0.583 | Destabilizing | 0.999 | D | 0.771 | deleterious | None | None | None | None | N |
| T/G | 0.4257 | ambiguous | 0.4353 | ambiguous | -1.083 | Destabilizing | 0.992 | D | 0.659 | neutral | None | None | None | None | N |
| T/H | 0.4478 | ambiguous | 0.4376 | ambiguous | -1.415 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| T/I | 0.2712 | likely_benign | 0.2691 | benign | -0.046 | Destabilizing | 0.999 | D | 0.754 | deleterious | N | 0.516713507 | None | None | N |
| T/K | 0.2554 | likely_benign | 0.2587 | benign | -1.082 | Destabilizing | 0.437 | N | 0.281 | neutral | None | None | None | None | N |
| T/L | 0.1432 | likely_benign | 0.1479 | benign | -0.046 | Destabilizing | 0.992 | D | 0.591 | neutral | None | None | None | None | N |
| T/M | 0.1418 | likely_benign | 0.1312 | benign | 0.226 | Stabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | None | N |
| T/N | 0.2181 | likely_benign | 0.2238 | benign | -1.029 | Destabilizing | 0.997 | D | 0.623 | neutral | N | 0.486527433 | None | None | N |
| T/P | 0.6388 | likely_pathogenic | 0.659 | pathogenic | -0.259 | Destabilizing | 0.999 | D | 0.745 | deleterious | N | 0.510672075 | None | None | N |
| T/Q | 0.3203 | likely_benign | 0.3193 | benign | -1.097 | Destabilizing | 0.995 | D | 0.754 | deleterious | None | None | None | None | N |
| T/R | 0.275 | likely_benign | 0.2673 | benign | -0.902 | Destabilizing | 0.99 | D | 0.679 | prob.neutral | None | None | None | None | N |
| T/S | 0.1724 | likely_benign | 0.1661 | benign | -1.185 | Destabilizing | 0.978 | D | 0.449 | neutral | N | 0.516750792 | None | None | N |
| T/V | 0.2264 | likely_benign | 0.2318 | benign | -0.259 | Destabilizing | 0.992 | D | 0.517 | neutral | None | None | None | None | N |
| T/W | 0.8273 | likely_pathogenic | 0.8237 | pathogenic | -0.628 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| T/Y | 0.5432 | ambiguous | 0.5555 | ambiguous | -0.422 | Destabilizing | 0.999 | D | 0.771 | 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.