Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15354 | 46285;46286;46287 | chr2:178620461;178620460;178620459 | chr2:179485188;179485187;179485186 |
| N2AB | 13713 | 41362;41363;41364 | chr2:178620461;178620460;178620459 | chr2:179485188;179485187;179485186 |
| N2A | 12786 | 38581;38582;38583 | chr2:178620461;178620460;178620459 | chr2:179485188;179485187;179485186 |
| N2B | 6289 | 19090;19091;19092 | chr2:178620461;178620460;178620459 | chr2:179485188;179485187;179485186 |
| Novex-1 | 6414 | 19465;19466;19467 | chr2:178620461;178620460;178620459 | chr2:179485188;179485187;179485186 |
| Novex-2 | 6481 | 19666;19667;19668 | chr2:178620461;178620460;178620459 | chr2:179485188;179485187;179485186 |
| 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 | rs886038861  |
-0.551 | 0.993 | N | 0.464 | 0.381 | 0.601175442443 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| Y/C | rs886038861 |
-0.551 | 0.993 | N | 0.464 | 0.381 | 0.601175442443 | gnomAD-4.0.0 | 1.3695E-05 | None | None | None | None | N | None | 5.99089E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.62004E-05 | 0 | 0 |
| Y/H | rs1324351583 |
-0.719 | 0.975 | N | 0.404 | 0.287 | 0.412328234245 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/H | rs1324351583 |
-0.719 | 0.975 | N | 0.404 | 0.287 | 0.412328234245 | gnomAD-4.0.0 | 1.09562E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.26005E-05 | 0 | 3.31697E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.6233 | likely_pathogenic | 0.6026 | pathogenic | -2.2 | Highly Destabilizing | 0.495 | N | 0.443 | neutral | None | None | None | None | N |
| Y/C | 0.2044 | likely_benign | 0.2134 | benign | -0.808 | Destabilizing | 0.993 | D | 0.464 | neutral | N | 0.490068566 | None | None | N |
| Y/D | 0.3061 | likely_benign | 0.2325 | benign | -0.924 | Destabilizing | 0.002 | N | 0.266 | neutral | N | 0.396232036 | None | None | N |
| Y/E | 0.6327 | likely_pathogenic | 0.5938 | pathogenic | -0.844 | Destabilizing | 0.031 | N | 0.269 | neutral | None | None | None | None | N |
| Y/F | 0.12 | likely_benign | 0.1532 | benign | -0.949 | Destabilizing | 0.006 | N | 0.138 | neutral | N | 0.454896956 | None | None | N |
| Y/G | 0.428 | ambiguous | 0.3662 | ambiguous | -2.515 | Highly Destabilizing | 0.828 | D | 0.48 | neutral | None | None | None | None | N |
| Y/H | 0.301 | likely_benign | 0.2554 | benign | -0.947 | Destabilizing | 0.975 | D | 0.404 | neutral | N | 0.489233319 | None | None | N |
| Y/I | 0.6693 | likely_pathogenic | 0.696 | pathogenic | -1.25 | Destabilizing | 0.543 | D | 0.447 | neutral | None | None | None | None | N |
| Y/K | 0.7054 | likely_pathogenic | 0.6155 | pathogenic | -1.185 | Destabilizing | 0.031 | N | 0.291 | neutral | None | None | None | None | N |
| Y/L | 0.5108 | ambiguous | 0.4998 | ambiguous | -1.25 | Destabilizing | 0.329 | N | 0.375 | neutral | None | None | None | None | N |
| Y/M | 0.6003 | likely_pathogenic | 0.63 | pathogenic | -0.843 | Destabilizing | 0.944 | D | 0.448 | neutral | None | None | None | None | N |
| Y/N | 0.1541 | likely_benign | 0.1127 | benign | -1.534 | Destabilizing | 0.642 | D | 0.483 | neutral | N | 0.479638488 | None | None | N |
| Y/P | 0.903 | likely_pathogenic | 0.8916 | pathogenic | -1.562 | Destabilizing | 0.981 | D | 0.51 | neutral | None | None | None | None | N |
| Y/Q | 0.5843 | likely_pathogenic | 0.5233 | ambiguous | -1.452 | Destabilizing | 0.704 | D | 0.457 | neutral | None | None | None | None | N |
| Y/R | 0.6146 | likely_pathogenic | 0.5389 | ambiguous | -0.741 | Destabilizing | 0.543 | D | 0.505 | neutral | None | None | None | None | N |
| Y/S | 0.3388 | likely_benign | 0.2864 | benign | -2.007 | Highly Destabilizing | 0.642 | D | 0.444 | neutral | N | 0.441132102 | None | None | N |
| Y/T | 0.5546 | ambiguous | 0.5088 | ambiguous | -1.833 | Destabilizing | 0.828 | D | 0.472 | neutral | None | None | None | None | N |
| Y/V | 0.5457 | ambiguous | 0.5647 | pathogenic | -1.562 | Destabilizing | 0.704 | D | 0.407 | neutral | None | None | None | None | N |
| Y/W | 0.4618 | ambiguous | 0.546 | ambiguous | -0.604 | Destabilizing | 0.995 | D | 0.429 | 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.