Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35686 | 107281;107282;107283 | chr2:178528695;178528694;178528693 | chr2:179393422;179393421;179393420 |
| N2AB | 34045 | 102358;102359;102360 | chr2:178528695;178528694;178528693 | chr2:179393422;179393421;179393420 |
| N2A | 33118 | 99577;99578;99579 | chr2:178528695;178528694;178528693 | chr2:179393422;179393421;179393420 |
| N2B | 26621 | 80086;80087;80088 | chr2:178528695;178528694;178528693 | chr2:179393422;179393421;179393420 |
| Novex-1 | 26746 | 80461;80462;80463 | chr2:178528695;178528694;178528693 | chr2:179393422;179393421;179393420 |
| Novex-2 | 26813 | 80662;80663;80664 | chr2:178528695;178528694;178528693 | chr2:179393422;179393421;179393420 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/G | None | None | 0.497 | N | 0.611 | 0.312 | 0.661173699051 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs751581732  |
-0.09 | 0.002 | N | 0.109 | 0.167 | 0.137902524267 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | I | None | 6.49E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.46E-05 | 0 |
| V/I | rs751581732 |
-0.09 | 0.002 | N | 0.109 | 0.167 | 0.137902524267 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 2.06868E-04 | 0 |
| V/I | rs751581732 |
-0.09 | 0.002 | N | 0.109 | 0.167 | 0.137902524267 | gnomAD-4.0.0 | 3.59507E-05 | None | None | None | None | I | None | 4.0047E-05 | 0 | None | 0 | 1.33696E-04 | None | 1.56367E-05 | 0 | 3.98421E-05 | 1.09888E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3611 | ambiguous | 0.3251 | benign | -1.767 | Destabilizing | 0.055 | N | 0.391 | neutral | N | 0.467410555 | None | None | I |
| V/C | 0.8617 | likely_pathogenic | 0.8594 | pathogenic | -1.337 | Destabilizing | 0.968 | D | 0.521 | neutral | None | None | None | None | I |
| V/D | 0.6969 | likely_pathogenic | 0.6543 | pathogenic | -1.64 | Destabilizing | 0.497 | N | 0.653 | neutral | N | 0.468797422 | None | None | I |
| V/E | 0.5163 | ambiguous | 0.4443 | ambiguous | -1.579 | Destabilizing | 0.567 | D | 0.603 | neutral | None | None | None | None | I |
| V/F | 0.219 | likely_benign | 0.1975 | benign | -1.203 | Destabilizing | 0.715 | D | 0.532 | neutral | N | 0.470704363 | None | None | I |
| V/G | 0.4693 | ambiguous | 0.4435 | ambiguous | -2.156 | Highly Destabilizing | 0.497 | N | 0.611 | neutral | N | 0.470357647 | None | None | I |
| V/H | 0.7107 | likely_pathogenic | 0.6715 | pathogenic | -1.676 | Destabilizing | 0.968 | D | 0.658 | neutral | None | None | None | None | I |
| V/I | 0.0669 | likely_benign | 0.0698 | benign | -0.762 | Destabilizing | 0.002 | N | 0.109 | neutral | N | 0.432916766 | None | None | I |
| V/K | 0.4948 | ambiguous | 0.4314 | ambiguous | -1.423 | Destabilizing | 0.567 | D | 0.615 | neutral | None | None | None | None | I |
| V/L | 0.2051 | likely_benign | 0.1852 | benign | -0.762 | Destabilizing | 0.022 | N | 0.354 | neutral | N | 0.469837572 | None | None | I |
| V/M | 0.1819 | likely_benign | 0.1643 | benign | -0.673 | Destabilizing | 0.567 | D | 0.499 | neutral | None | None | None | None | I |
| V/N | 0.4953 | ambiguous | 0.4651 | ambiguous | -1.319 | Destabilizing | 0.567 | D | 0.667 | neutral | None | None | None | None | I |
| V/P | 0.9329 | likely_pathogenic | 0.9413 | pathogenic | -1.064 | Destabilizing | 0.726 | D | 0.654 | neutral | None | None | None | None | I |
| V/Q | 0.4816 | ambiguous | 0.4163 | ambiguous | -1.413 | Destabilizing | 0.726 | D | 0.652 | neutral | None | None | None | None | I |
| V/R | 0.4178 | ambiguous | 0.3685 | ambiguous | -1.005 | Destabilizing | 0.567 | D | 0.669 | neutral | None | None | None | None | I |
| V/S | 0.391 | ambiguous | 0.354 | ambiguous | -1.946 | Destabilizing | 0.157 | N | 0.579 | neutral | None | None | None | None | I |
| V/T | 0.3013 | likely_benign | 0.2723 | benign | -1.765 | Destabilizing | 0.001 | N | 0.207 | neutral | None | None | None | None | I |
| V/W | 0.8583 | likely_pathogenic | 0.8331 | pathogenic | -1.445 | Destabilizing | 0.968 | D | 0.726 | prob.delet. | None | None | None | None | I |
| V/Y | 0.63 | likely_pathogenic | 0.5892 | pathogenic | -1.15 | Destabilizing | 0.726 | D | 0.529 | 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.