Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21252 | 63979;63980;63981 | chr2:178587555;178587554;178587553 | chr2:179452282;179452281;179452280 |
| N2AB | 19611 | 59056;59057;59058 | chr2:178587555;178587554;178587553 | chr2:179452282;179452281;179452280 |
| N2A | 18684 | 56275;56276;56277 | chr2:178587555;178587554;178587553 | chr2:179452282;179452281;179452280 |
| N2B | 12187 | 36784;36785;36786 | chr2:178587555;178587554;178587553 | chr2:179452282;179452281;179452280 |
| Novex-1 | 12312 | 37159;37160;37161 | chr2:178587555;178587554;178587553 | chr2:179452282;179452281;179452280 |
| Novex-2 | 12379 | 37360;37361;37362 | chr2:178587555;178587554;178587553 | chr2:179452282;179452281;179452280 |
| 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/P | rs1414305945  |
-0.189 | 0.999 | D | 0.701 | 0.514 | 0.464442853059 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| A/P | rs1414305945 |
-0.189 | 0.999 | D | 0.701 | 0.514 | 0.464442853059 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/P | rs1414305945 |
-0.189 | 0.999 | D | 0.701 | 0.514 | 0.464442853059 | gnomAD-4.0.0 | 6.58085E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47098E-05 | 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 | 0.4095 | ambiguous | 0.4299 | ambiguous | -0.847 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| A/D | 0.7133 | likely_pathogenic | 0.6924 | pathogenic | -0.561 | Destabilizing | 0.998 | D | 0.721 | prob.delet. | None | None | None | None | I |
| A/E | 0.6163 | likely_pathogenic | 0.597 | pathogenic | -0.71 | Destabilizing | 0.998 | D | 0.673 | neutral | N | 0.504561188 | None | None | I |
| A/F | 0.5195 | ambiguous | 0.5215 | ambiguous | -0.952 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| A/G | 0.2281 | likely_benign | 0.231 | benign | -0.251 | Destabilizing | 0.992 | D | 0.599 | neutral | N | 0.488152 | None | None | I |
| A/H | 0.6889 | likely_pathogenic | 0.6812 | pathogenic | -0.254 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | I |
| A/I | 0.3692 | ambiguous | 0.386 | ambiguous | -0.44 | Destabilizing | 0.999 | D | 0.695 | prob.neutral | None | None | None | None | I |
| A/K | 0.7926 | likely_pathogenic | 0.7711 | pathogenic | -0.568 | Destabilizing | 0.998 | D | 0.677 | prob.neutral | None | None | None | None | I |
| A/L | 0.352 | ambiguous | 0.3636 | ambiguous | -0.44 | Destabilizing | 0.997 | D | 0.654 | neutral | None | None | None | None | I |
| A/M | 0.3534 | ambiguous | 0.3711 | ambiguous | -0.589 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | I |
| A/N | 0.5705 | likely_pathogenic | 0.5649 | pathogenic | -0.267 | Destabilizing | 0.998 | D | 0.725 | prob.delet. | None | None | None | None | I |
| A/P | 0.8804 | likely_pathogenic | 0.8702 | pathogenic | -0.353 | Destabilizing | 0.999 | D | 0.701 | prob.neutral | D | 0.528034267 | None | None | I |
| A/Q | 0.5894 | likely_pathogenic | 0.5856 | pathogenic | -0.526 | Destabilizing | 0.999 | D | 0.707 | prob.neutral | None | None | None | None | I |
| A/R | 0.7196 | likely_pathogenic | 0.6891 | pathogenic | -0.144 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | I |
| A/S | 0.1159 | likely_benign | 0.1145 | benign | -0.445 | Destabilizing | 0.916 | D | 0.573 | neutral | N | 0.446325994 | None | None | I |
| A/T | 0.1538 | likely_benign | 0.15 | benign | -0.523 | Destabilizing | 0.984 | D | 0.66 | neutral | N | 0.504165886 | None | None | I |
| A/V | 0.1555 | likely_benign | 0.1586 | benign | -0.353 | Destabilizing | 0.996 | D | 0.667 | neutral | N | 0.509046534 | None | None | I |
| A/W | 0.8959 | likely_pathogenic | 0.8981 | pathogenic | -1.05 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| A/Y | 0.6946 | likely_pathogenic | 0.6947 | pathogenic | -0.74 | Destabilizing | 1.0 | D | 0.74 | deleterious | 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.