Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25757 | 77494;77495;77496 | chr2:178568863;178568862;178568861 | chr2:179433590;179433589;179433588 |
| N2AB | 24116 | 72571;72572;72573 | chr2:178568863;178568862;178568861 | chr2:179433590;179433589;179433588 |
| N2A | 23189 | 69790;69791;69792 | chr2:178568863;178568862;178568861 | chr2:179433590;179433589;179433588 |
| N2B | 16692 | 50299;50300;50301 | chr2:178568863;178568862;178568861 | chr2:179433590;179433589;179433588 |
| Novex-1 | 16817 | 50674;50675;50676 | chr2:178568863;178568862;178568861 | chr2:179433590;179433589;179433588 |
| Novex-2 | 16884 | 50875;50876;50877 | chr2:178568863;178568862;178568861 | chr2:179433590;179433589;179433588 |
| 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/A | rs888818269  |
None | 0.472 | N | 0.437 | 0.129 | 0.520694202979 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs888818269 |
None | 0.472 | N | 0.437 | 0.129 | 0.520694202979 | gnomAD-4.0.0 | 1.85984E-06 | None | None | None | None | N | None | 4.00598E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/E | None | None | 0.007 | N | 0.441 | 0.255 | 0.648112553962 | gnomAD-4.0.0 | 6.84488E-07 | None | None | None | None | N | None | 0 | 0 | None | 3.82907E-05 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs1307639752 |
0.011 | 0.007 | N | 0.255 | 0.088 | 0.415820034956 | gnomAD-4.0.0 | 1.59281E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85953E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1739 | likely_benign | 0.1623 | benign | -0.565 | Destabilizing | 0.472 | N | 0.437 | neutral | N | 0.504954931 | None | None | N |
| V/C | 0.6869 | likely_pathogenic | 0.6641 | pathogenic | -0.705 | Destabilizing | 0.996 | D | 0.567 | neutral | None | None | None | None | N |
| V/D | 0.3234 | likely_benign | 0.2922 | benign | -0.151 | Destabilizing | 0.59 | D | 0.618 | neutral | None | None | None | None | N |
| V/E | 0.2047 | likely_benign | 0.1915 | benign | -0.248 | Destabilizing | 0.007 | N | 0.441 | neutral | N | 0.484424943 | None | None | N |
| V/F | 0.1944 | likely_benign | 0.1923 | benign | -0.676 | Destabilizing | 0.91 | D | 0.589 | neutral | None | None | None | None | N |
| V/G | 0.2501 | likely_benign | 0.2312 | benign | -0.726 | Destabilizing | 0.684 | D | 0.607 | neutral | N | 0.480700855 | None | None | N |
| V/H | 0.451 | ambiguous | 0.4262 | ambiguous | -0.277 | Destabilizing | 0.987 | D | 0.623 | neutral | None | None | None | None | N |
| V/I | 0.0772 | likely_benign | 0.0775 | benign | -0.288 | Destabilizing | 0.521 | D | 0.432 | neutral | D | 0.524271411 | None | None | N |
| V/K | 0.2369 | likely_benign | 0.2188 | benign | -0.48 | Destabilizing | 0.037 | N | 0.441 | neutral | None | None | None | None | N |
| V/L | 0.1666 | likely_benign | 0.1625 | benign | -0.288 | Destabilizing | 0.007 | N | 0.255 | neutral | N | 0.503704137 | None | None | N |
| V/M | 0.1168 | likely_benign | 0.113 | benign | -0.344 | Destabilizing | 0.91 | D | 0.513 | neutral | None | None | None | None | N |
| V/N | 0.1913 | likely_benign | 0.1722 | benign | -0.26 | Destabilizing | 0.91 | D | 0.631 | neutral | None | None | None | None | N |
| V/P | 0.7738 | likely_pathogenic | 0.7457 | pathogenic | -0.345 | Destabilizing | 0.953 | D | 0.649 | neutral | None | None | None | None | N |
| V/Q | 0.2214 | likely_benign | 0.2106 | benign | -0.476 | Destabilizing | 0.835 | D | 0.643 | neutral | None | None | None | None | N |
| V/R | 0.2565 | likely_benign | 0.249 | benign | 0.008 | Stabilizing | 0.835 | D | 0.638 | neutral | None | None | None | None | N |
| V/S | 0.1796 | likely_benign | 0.1637 | benign | -0.681 | Destabilizing | 0.59 | D | 0.56 | neutral | None | None | None | None | N |
| V/T | 0.1113 | likely_benign | 0.1016 | benign | -0.67 | Destabilizing | 0.037 | N | 0.362 | neutral | None | None | None | None | N |
| V/W | 0.8377 | likely_pathogenic | 0.8288 | pathogenic | -0.759 | Destabilizing | 0.996 | D | 0.682 | prob.neutral | None | None | None | None | N |
| V/Y | 0.5448 | ambiguous | 0.5206 | ambiguous | -0.458 | Destabilizing | 0.953 | D | 0.587 | 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.