Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29645 | 89158;89159;89160 | chr2:178554178;178554177;178554176 | chr2:179418905;179418904;179418903 |
| N2AB | 28004 | 84235;84236;84237 | chr2:178554178;178554177;178554176 | chr2:179418905;179418904;179418903 |
| N2A | 27077 | 81454;81455;81456 | chr2:178554178;178554177;178554176 | chr2:179418905;179418904;179418903 |
| N2B | 20580 | 61963;61964;61965 | chr2:178554178;178554177;178554176 | chr2:179418905;179418904;179418903 |
| Novex-1 | 20705 | 62338;62339;62340 | chr2:178554178;178554177;178554176 | chr2:179418905;179418904;179418903 |
| Novex-2 | 20772 | 62539;62540;62541 | chr2:178554178;178554177;178554176 | chr2:179418905;179418904;179418903 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/F | rs746067385  |
-1.63 | 0.81 | D | 0.375 | 0.204 | 0.411932830014 | gnomAD-2.1.1 | 4.12E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.14E-06 | 0 |
| I/F | rs746067385 |
-1.63 | 0.81 | D | 0.375 | 0.204 | 0.411932830014 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/F | rs746067385 |
-1.63 | 0.81 | D | 0.375 | 0.204 | 0.411932830014 | gnomAD-4.0.0 | 6.83497E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.48719E-06 | 0 | 1.60601E-05 |
| I/T | rs774597895 |
-1.603 | 0.004 | N | 0.203 | 0.082 | 0.306377322295 | gnomAD-2.1.1 | 1.65E-05 | None | None | None | None | N | None | 0 | 1.18231E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs774597895 |
-1.603 | 0.004 | N | 0.203 | 0.082 | 0.306377322295 | gnomAD-4.0.0 | 8.01218E-06 | None | None | None | None | N | None | 0 | 1.16128E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.423 | ambiguous | 0.5412 | ambiguous | -1.774 | Destabilizing | 0.25 | N | 0.381 | neutral | None | None | None | None | N |
| I/C | 0.6274 | likely_pathogenic | 0.696 | pathogenic | -1.444 | Destabilizing | 0.992 | D | 0.307 | neutral | None | None | None | None | N |
| I/D | 0.8489 | likely_pathogenic | 0.9107 | pathogenic | -1.749 | Destabilizing | 0.85 | D | 0.437 | neutral | None | None | None | None | N |
| I/E | 0.7217 | likely_pathogenic | 0.8035 | pathogenic | -1.749 | Destabilizing | 0.85 | D | 0.445 | neutral | None | None | None | None | N |
| I/F | 0.2833 | likely_benign | 0.4262 | ambiguous | -1.594 | Destabilizing | 0.81 | D | 0.375 | neutral | D | 0.522890118 | None | None | N |
| I/G | 0.7317 | likely_pathogenic | 0.8298 | pathogenic | -2.078 | Highly Destabilizing | 0.447 | N | 0.431 | neutral | None | None | None | None | N |
| I/H | 0.6745 | likely_pathogenic | 0.7827 | pathogenic | -1.44 | Destabilizing | 0.977 | D | 0.407 | neutral | None | None | None | None | N |
| I/K | 0.4827 | ambiguous | 0.5927 | pathogenic | -1.155 | Destabilizing | 0.447 | N | 0.445 | neutral | None | None | None | None | N |
| I/L | 0.193 | likely_benign | 0.2537 | benign | -1.002 | Destabilizing | 0.036 | N | 0.249 | neutral | N | 0.499703827 | None | None | N |
| I/M | 0.1139 | likely_benign | 0.1596 | benign | -0.823 | Destabilizing | 0.036 | N | 0.273 | neutral | N | 0.477804474 | None | None | N |
| I/N | 0.3631 | ambiguous | 0.4594 | ambiguous | -1.074 | Destabilizing | 0.681 | D | 0.445 | neutral | N | 0.477044005 | None | None | N |
| I/P | 0.8059 | likely_pathogenic | 0.8565 | pathogenic | -1.231 | Destabilizing | 0.92 | D | 0.459 | neutral | None | None | None | None | N |
| I/Q | 0.5397 | ambiguous | 0.6412 | pathogenic | -1.315 | Destabilizing | 0.85 | D | 0.458 | neutral | None | None | None | None | N |
| I/R | 0.3873 | ambiguous | 0.5088 | ambiguous | -0.606 | Destabilizing | 0.85 | D | 0.46 | neutral | None | None | None | None | N |
| I/S | 0.3763 | ambiguous | 0.4871 | ambiguous | -1.663 | Destabilizing | 0.016 | N | 0.271 | neutral | N | 0.457915919 | None | None | N |
| I/T | 0.2606 | likely_benign | 0.3572 | ambiguous | -1.548 | Destabilizing | 0.004 | N | 0.203 | neutral | N | 0.443754544 | None | None | N |
| I/V | 0.0944 | likely_benign | 0.1005 | benign | -1.231 | Destabilizing | 0.016 | N | 0.097 | neutral | N | 0.37804684 | None | None | N |
| I/W | 0.8385 | likely_pathogenic | 0.9118 | pathogenic | -1.686 | Destabilizing | 0.992 | D | 0.501 | neutral | None | None | None | None | N |
| I/Y | 0.5848 | likely_pathogenic | 0.7117 | pathogenic | -1.394 | Destabilizing | 0.92 | D | 0.359 | 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.