Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35194 | 105805;105806;105807 | chr2:178531035;178531034;178531033 | chr2:179395762;179395761;179395760 |
| N2AB | 33553 | 100882;100883;100884 | chr2:178531035;178531034;178531033 | chr2:179395762;179395761;179395760 |
| N2A | 32626 | 98101;98102;98103 | chr2:178531035;178531034;178531033 | chr2:179395762;179395761;179395760 |
| N2B | 26129 | 78610;78611;78612 | chr2:178531035;178531034;178531033 | chr2:179395762;179395761;179395760 |
| Novex-1 | 26254 | 78985;78986;78987 | chr2:178531035;178531034;178531033 | chr2:179395762;179395761;179395760 |
| Novex-2 | 26321 | 79186;79187;79188 | chr2:178531035;178531034;178531033 | chr2:179395762;179395761;179395760 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/T | rs1269069525  |
-0.66 | 0.722 | N | 0.425 | 0.163 | 0.187945064343 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/T | rs1269069525 |
-0.66 | 0.722 | N | 0.425 | 0.163 | 0.187945064343 | gnomAD-4.0.0 | 1.59088E-06 | None | None | None | None | N | None | 5.65227E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0733 | likely_benign | 0.0761 | benign | -0.279 | Destabilizing | 0.008 | N | 0.179 | neutral | N | 0.465849464 | None | None | N |
| S/C | 0.2193 | likely_benign | 0.2017 | benign | -0.285 | Destabilizing | 0.986 | D | 0.512 | neutral | N | 0.509946108 | None | None | N |
| S/D | 0.3233 | likely_benign | 0.3574 | ambiguous | -0.024 | Destabilizing | 0.961 | D | 0.41 | neutral | None | None | None | None | N |
| S/E | 0.3814 | ambiguous | 0.4136 | ambiguous | -0.135 | Destabilizing | 0.775 | D | 0.399 | neutral | None | None | None | None | N |
| S/F | 0.1923 | likely_benign | 0.216 | benign | -0.986 | Destabilizing | 0.018 | N | 0.267 | neutral | N | 0.483194573 | None | None | N |
| S/G | 0.1114 | likely_benign | 0.1165 | benign | -0.344 | Destabilizing | 0.633 | D | 0.403 | neutral | None | None | None | None | N |
| S/H | 0.3987 | ambiguous | 0.426 | ambiguous | -0.797 | Destabilizing | 0.996 | D | 0.494 | neutral | None | None | None | None | N |
| S/I | 0.1973 | likely_benign | 0.1906 | benign | -0.242 | Destabilizing | 0.858 | D | 0.52 | neutral | None | None | None | None | N |
| S/K | 0.6013 | likely_pathogenic | 0.6238 | pathogenic | -0.432 | Destabilizing | 0.775 | D | 0.4 | neutral | None | None | None | None | N |
| S/L | 0.1071 | likely_benign | 0.1113 | benign | -0.242 | Destabilizing | 0.633 | D | 0.449 | neutral | None | None | None | None | N |
| S/M | 0.2298 | likely_benign | 0.2284 | benign | -0.014 | Destabilizing | 0.989 | D | 0.491 | neutral | None | None | None | None | N |
| S/N | 0.167 | likely_benign | 0.1698 | benign | -0.182 | Destabilizing | 0.961 | D | 0.446 | neutral | None | None | None | None | N |
| S/P | 0.2399 | likely_benign | 0.2589 | benign | -0.229 | Destabilizing | 0.949 | D | 0.463 | neutral | N | 0.475205629 | None | None | N |
| S/Q | 0.4824 | ambiguous | 0.5091 | ambiguous | -0.452 | Destabilizing | 0.961 | D | 0.429 | neutral | None | None | None | None | N |
| S/R | 0.5038 | ambiguous | 0.535 | ambiguous | -0.178 | Destabilizing | 0.923 | D | 0.464 | neutral | None | None | None | None | N |
| S/T | 0.0897 | likely_benign | 0.0923 | benign | -0.285 | Destabilizing | 0.722 | D | 0.425 | neutral | N | 0.513064621 | None | None | N |
| S/V | 0.1984 | likely_benign | 0.1981 | benign | -0.229 | Destabilizing | 0.633 | D | 0.459 | neutral | None | None | None | None | N |
| S/W | 0.2815 | likely_benign | 0.3265 | benign | -1.026 | Destabilizing | 0.996 | D | 0.685 | prob.neutral | None | None | None | None | N |
| S/Y | 0.2157 | likely_benign | 0.2406 | benign | -0.731 | Destabilizing | 0.82 | D | 0.587 | neutral | N | 0.473648693 | 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.