Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18465 | 55618;55619;55620 | chr2:178601697;178601696;178601695 | chr2:179466424;179466423;179466422 |
| N2AB | 16824 | 50695;50696;50697 | chr2:178601697;178601696;178601695 | chr2:179466424;179466423;179466422 |
| N2A | 15897 | 47914;47915;47916 | chr2:178601697;178601696;178601695 | chr2:179466424;179466423;179466422 |
| N2B | 9400 | 28423;28424;28425 | chr2:178601697;178601696;178601695 | chr2:179466424;179466423;179466422 |
| Novex-1 | 9525 | 28798;28799;28800 | chr2:178601697;178601696;178601695 | chr2:179466424;179466423;179466422 |
| Novex-2 | 9592 | 28999;29000;29001 | chr2:178601697;178601696;178601695 | chr2:179466424;179466423;179466422 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/E | rs1375595248  |
-0.402 | 0.978 | N | 0.57 | 0.594 | 0.493156425868 | gnomAD-2.1.1 | 4.1E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.7E-05 | None | 0 | None | 0 | 0 | 0 |
| A/E | rs1375595248 |
-0.402 | 0.978 | N | 0.57 | 0.594 | 0.493156425868 | gnomAD-4.0.0 | 4.81413E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 8.3505E-05 | None | 0 | 0 | 0 | 0 | 0 |
| A/S | rs899078606 |
-0.19 | 0.418 | N | 0.389 | 0.095 | None | gnomAD-2.1.1 | 2.05E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.5E-05 | 0 |
| A/S | rs899078606 |
-0.19 | 0.418 | N | 0.389 | 0.095 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.89E-05 | 0 | 0 |
| A/S | rs899078606 |
-0.19 | 0.418 | N | 0.389 | 0.095 | None | gnomAD-4.0.0 | 2.98436E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.98897E-05 | 0 | 1.60777E-05 |
| A/T | rs899078606 |
-0.261 | 0.956 | N | 0.541 | 0.376 | 0.342631996419 | gnomAD-2.1.1 | 8.2E-06 | None | None | None | None | I | None | 0 | 5.94E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/T | rs899078606 |
-0.261 | 0.956 | N | 0.541 | 0.376 | 0.342631996419 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs899078606 |
-0.261 | 0.956 | N | 0.541 | 0.376 | 0.342631996419 | gnomAD-4.0.0 | 1.86523E-06 | None | None | None | None | I | None | 0 | 5.07838E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.4556 | ambiguous | 0.4404 | ambiguous | -0.922 | Destabilizing | 1.0 | D | 0.619 | neutral | None | None | None | None | I |
| A/D | 0.7017 | likely_pathogenic | 0.6608 | pathogenic | -0.556 | Destabilizing | 0.995 | D | 0.573 | neutral | None | None | None | None | I |
| A/E | 0.6279 | likely_pathogenic | 0.581 | pathogenic | -0.698 | Destabilizing | 0.978 | D | 0.57 | neutral | N | 0.508017455 | None | None | I |
| A/F | 0.3979 | ambiguous | 0.3611 | ambiguous | -0.959 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | I |
| A/G | 0.2428 | likely_benign | 0.2339 | benign | -0.299 | Destabilizing | 0.948 | D | 0.551 | neutral | N | 0.502968711 | None | None | I |
| A/H | 0.6592 | likely_pathogenic | 0.6044 | pathogenic | -0.252 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | I |
| A/I | 0.3765 | ambiguous | 0.3478 | ambiguous | -0.483 | Destabilizing | 0.998 | D | 0.614 | neutral | None | None | None | None | I |
| A/K | 0.7896 | likely_pathogenic | 0.7119 | pathogenic | -0.594 | Destabilizing | 0.983 | D | 0.575 | neutral | None | None | None | None | I |
| A/L | 0.3589 | ambiguous | 0.3113 | benign | -0.483 | Destabilizing | 0.992 | D | 0.609 | neutral | None | None | None | None | I |
| A/M | 0.3552 | ambiguous | 0.3127 | benign | -0.656 | Destabilizing | 1.0 | D | 0.614 | neutral | None | None | None | None | I |
| A/N | 0.5283 | ambiguous | 0.4974 | ambiguous | -0.325 | Destabilizing | 0.995 | D | 0.595 | neutral | None | None | None | None | I |
| A/P | 0.9061 | likely_pathogenic | 0.9075 | pathogenic | -0.399 | Destabilizing | 0.997 | D | 0.614 | neutral | N | 0.508777923 | None | None | I |
| A/Q | 0.6324 | likely_pathogenic | 0.5648 | pathogenic | -0.567 | Destabilizing | 0.998 | D | 0.604 | neutral | None | None | None | None | I |
| A/R | 0.7167 | likely_pathogenic | 0.6227 | pathogenic | -0.175 | Destabilizing | 0.998 | D | 0.61 | neutral | None | None | None | None | I |
| A/S | 0.1234 | likely_benign | 0.1241 | benign | -0.52 | Destabilizing | 0.418 | N | 0.389 | neutral | N | 0.454406759 | None | None | I |
| A/T | 0.1516 | likely_benign | 0.151 | benign | -0.589 | Destabilizing | 0.956 | D | 0.541 | neutral | N | 0.505482559 | None | None | I |
| A/V | 0.1669 | likely_benign | 0.1579 | benign | -0.399 | Destabilizing | 0.989 | D | 0.57 | neutral | N | 0.491807567 | None | None | I |
| A/W | 0.8276 | likely_pathogenic | 0.7772 | pathogenic | -1.044 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | I |
| A/Y | 0.5715 | likely_pathogenic | 0.5159 | ambiguous | -0.749 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | I |
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.