Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29269 | 88030;88031;88032 | chr2:178557457;178557456;178557455 | chr2:179422184;179422183;179422182 |
| N2AB | 27628 | 83107;83108;83109 | chr2:178557457;178557456;178557455 | chr2:179422184;179422183;179422182 |
| N2A | 26701 | 80326;80327;80328 | chr2:178557457;178557456;178557455 | chr2:179422184;179422183;179422182 |
| N2B | 20204 | 60835;60836;60837 | chr2:178557457;178557456;178557455 | chr2:179422184;179422183;179422182 |
| Novex-1 | 20329 | 61210;61211;61212 | chr2:178557457;178557456;178557455 | chr2:179422184;179422183;179422182 |
| Novex-2 | 20396 | 61411;61412;61413 | chr2:178557457;178557456;178557455 | chr2:179422184;179422183;179422182 |
| 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 | None | None | 0.977 | N | 0.662 | 0.466 | 0.634567249438 | gnomAD-4.0.0 | 1.36834E-06 | None | None | None | None | I | None | 5.97372E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs727503551  |
-0.726 | 0.117 | N | 0.337 | 0.074 | 0.422404719673 | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 9.8E-05 | None | 0 | 3.55E-05 | 0 |
| V/I | rs727503551 |
-0.726 | 0.117 | N | 0.337 | 0.074 | 0.422404719673 | gnomAD-3.1.2 | 3.28E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 6.32911E-03 | 4.41E-05 | 0 | 0 |
| V/I | rs727503551 |
-0.726 | 0.117 | N | 0.337 | 0.074 | 0.422404719673 | gnomAD-4.0.0 | 2.97405E-05 | None | None | None | None | I | None | 0 | 1.66594E-05 | None | 0 | 0 | None | 0 | 1.48515E-03 | 2.45791E-05 | 5.48932E-05 | 6.40164E-05 |
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 | 0.7311 | likely_pathogenic | 0.7398 | pathogenic | -1.703 | Destabilizing | 0.977 | D | 0.662 | neutral | N | 0.495553107 | None | None | I |
| V/C | 0.9566 | likely_pathogenic | 0.9593 | pathogenic | -1.117 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | I |
| V/D | 0.9917 | likely_pathogenic | 0.9913 | pathogenic | -1.587 | Destabilizing | 0.999 | D | 0.881 | deleterious | N | 0.488209273 | None | None | I |
| V/E | 0.9746 | likely_pathogenic | 0.975 | pathogenic | -1.556 | Destabilizing | 0.999 | D | 0.887 | deleterious | None | None | None | None | I |
| V/F | 0.8461 | likely_pathogenic | 0.8678 | pathogenic | -1.284 | Destabilizing | 0.993 | D | 0.881 | deleterious | N | 0.498298131 | None | None | I |
| V/G | 0.9172 | likely_pathogenic | 0.9223 | pathogenic | -2.065 | Highly Destabilizing | 0.999 | D | 0.866 | deleterious | N | 0.51944426 | None | None | I |
| V/H | 0.9936 | likely_pathogenic | 0.9939 | pathogenic | -1.606 | Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | I |
| V/I | 0.0758 | likely_benign | 0.0774 | benign | -0.79 | Destabilizing | 0.117 | N | 0.337 | neutral | N | 0.386604821 | None | None | I |
| V/K | 0.9845 | likely_pathogenic | 0.9837 | pathogenic | -1.419 | Destabilizing | 0.998 | D | 0.887 | deleterious | None | None | None | None | I |
| V/L | 0.4797 | ambiguous | 0.5262 | ambiguous | -0.79 | Destabilizing | 0.898 | D | 0.583 | neutral | N | 0.521924539 | None | None | I |
| V/M | 0.552 | ambiguous | 0.5998 | pathogenic | -0.569 | Destabilizing | 0.995 | D | 0.817 | deleterious | None | None | None | None | I |
| V/N | 0.9675 | likely_pathogenic | 0.964 | pathogenic | -1.237 | Destabilizing | 0.999 | D | 0.874 | deleterious | None | None | None | None | I |
| V/P | 0.8334 | likely_pathogenic | 0.8341 | pathogenic | -1.06 | Destabilizing | 0.999 | D | 0.899 | deleterious | None | None | None | None | I |
| V/Q | 0.9792 | likely_pathogenic | 0.9795 | pathogenic | -1.373 | Destabilizing | 0.999 | D | 0.888 | deleterious | None | None | None | None | I |
| V/R | 0.9758 | likely_pathogenic | 0.9756 | pathogenic | -0.904 | Destabilizing | 0.999 | D | 0.872 | deleterious | None | None | None | None | I |
| V/S | 0.9158 | likely_pathogenic | 0.9131 | pathogenic | -1.793 | Destabilizing | 0.998 | D | 0.891 | deleterious | None | None | None | None | I |
| V/T | 0.7068 | likely_pathogenic | 0.6941 | pathogenic | -1.645 | Destabilizing | 0.983 | D | 0.805 | deleterious | None | None | None | None | I |
| V/W | 0.9957 | likely_pathogenic | 0.9968 | pathogenic | -1.515 | Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | I |
| V/Y | 0.9855 | likely_pathogenic | 0.987 | pathogenic | -1.225 | Destabilizing | 0.999 | D | 0.881 | 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.