Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17164 | 51715;51716;51717 | chr2:178609933;178609932;178609931 | chr2:179474660;179474659;179474658 |
| N2AB | 15523 | 46792;46793;46794 | chr2:178609933;178609932;178609931 | chr2:179474660;179474659;179474658 |
| N2A | 14596 | 44011;44012;44013 | chr2:178609933;178609932;178609931 | chr2:179474660;179474659;179474658 |
| N2B | 8099 | 24520;24521;24522 | chr2:178609933;178609932;178609931 | chr2:179474660;179474659;179474658 |
| Novex-1 | 8224 | 24895;24896;24897 | chr2:178609933;178609932;178609931 | chr2:179474660;179474659;179474658 |
| Novex-2 | 8291 | 25096;25097;25098 | chr2:178609933;178609932;178609931 | chr2:179474660;179474659;179474658 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | None | None | None | N | 0.171 | 0.121 | 0.372087925617 | gnomAD-4.0.0 | 6.84538E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99819E-07 | 0 | 0 |
| M/T | rs1559765154  |
None | 0.002 | N | 0.439 | 0.309 | 0.724000541041 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 0 | 0 |
| M/T | rs1559765154 |
None | 0.002 | N | 0.439 | 0.309 | 0.724000541041 | gnomAD-4.0.0 | 1.36908E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.04592E-05 | None | 0 | 0 | 0 | 0 | 0 |
| M/V | rs922802371 |
None | None | N | 0.166 | 0.154 | 0.317084106153 | 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 |
| M/V | rs922802371 |
None | None | N | 0.166 | 0.154 | 0.317084106153 | gnomAD-4.0.0 | 2.48016E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39196E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.7414 | likely_pathogenic | 0.7202 | pathogenic | -1.977 | Destabilizing | 0.051 | N | 0.552 | neutral | None | None | None | None | N |
| M/C | 0.8037 | likely_pathogenic | 0.8025 | pathogenic | -2.422 | Highly Destabilizing | 0.968 | D | 0.735 | prob.delet. | None | None | None | None | N |
| M/D | 0.9987 | likely_pathogenic | 0.9983 | pathogenic | -2.05 | Highly Destabilizing | 0.738 | D | 0.713 | prob.delet. | None | None | None | None | N |
| M/E | 0.9871 | likely_pathogenic | 0.9833 | pathogenic | -1.862 | Destabilizing | 0.538 | D | 0.665 | neutral | None | None | None | None | N |
| M/F | 0.7544 | likely_pathogenic | 0.7337 | pathogenic | -0.714 | Destabilizing | 0.582 | D | 0.581 | neutral | None | None | None | None | N |
| M/G | 0.9685 | likely_pathogenic | 0.9622 | pathogenic | -2.422 | Highly Destabilizing | 0.538 | D | 0.663 | neutral | None | None | None | None | N |
| M/H | 0.9891 | likely_pathogenic | 0.9879 | pathogenic | -2.082 | Highly Destabilizing | 0.968 | D | 0.717 | prob.delet. | None | None | None | None | N |
| M/I | 0.5269 | ambiguous | 0.478 | ambiguous | -0.724 | Destabilizing | None | N | 0.171 | neutral | N | 0.346049064 | None | None | N |
| M/K | 0.9644 | likely_pathogenic | 0.9556 | pathogenic | -1.186 | Destabilizing | 0.468 | N | 0.666 | neutral | N | 0.467850066 | None | None | N |
| M/L | 0.3288 | likely_benign | 0.3253 | benign | -0.724 | Destabilizing | 0.017 | N | 0.305 | neutral | N | 0.38283101 | None | None | N |
| M/N | 0.9841 | likely_pathogenic | 0.9815 | pathogenic | -1.507 | Destabilizing | 0.738 | D | 0.731 | prob.delet. | None | None | None | None | N |
| M/P | 0.9984 | likely_pathogenic | 0.998 | pathogenic | -1.121 | Destabilizing | 0.896 | D | 0.73 | prob.delet. | None | None | None | None | N |
| M/Q | 0.9293 | likely_pathogenic | 0.9241 | pathogenic | -1.287 | Destabilizing | 0.896 | D | 0.648 | neutral | None | None | None | None | N |
| M/R | 0.9659 | likely_pathogenic | 0.9584 | pathogenic | -1.265 | Destabilizing | 0.68 | D | 0.735 | prob.delet. | N | 0.467850066 | None | None | N |
| M/S | 0.9177 | likely_pathogenic | 0.9092 | pathogenic | -2.059 | Highly Destabilizing | 0.223 | N | 0.564 | neutral | None | None | None | None | N |
| M/T | 0.7824 | likely_pathogenic | 0.7505 | pathogenic | -1.742 | Destabilizing | 0.002 | N | 0.439 | neutral | N | 0.465263179 | None | None | N |
| M/V | 0.1327 | likely_benign | 0.1184 | benign | -1.121 | Destabilizing | None | N | 0.166 | neutral | N | 0.327327231 | None | None | N |
| M/W | 0.9879 | likely_pathogenic | 0.9847 | pathogenic | -1.027 | Destabilizing | 0.991 | D | 0.716 | prob.delet. | None | None | None | None | N |
| M/Y | 0.9689 | likely_pathogenic | 0.9634 | pathogenic | -0.934 | Destabilizing | 0.738 | D | 0.737 | prob.delet. | 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.