Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3228 | 9907;9908;9909 | chr2:178766402;178766401;178766400 | chr2:179631129;179631128;179631127 |
| N2AB | 3228 | 9907;9908;9909 | chr2:178766402;178766401;178766400 | chr2:179631129;179631128;179631127 |
| N2A | 3228 | 9907;9908;9909 | chr2:178766402;178766401;178766400 | chr2:179631129;179631128;179631127 |
| N2B | 3182 | 9769;9770;9771 | chr2:178766402;178766401;178766400 | chr2:179631129;179631128;179631127 |
| Novex-1 | 3182 | 9769;9770;9771 | chr2:178766402;178766401;178766400 | chr2:179631129;179631128;179631127 |
| Novex-2 | 3182 | 9769;9770;9771 | chr2:178766402;178766401;178766400 | chr2:179631129;179631128;179631127 |
| Novex-3 | 3228 | 9907;9908;9909 | chr2:178766402;178766401;178766400 | chr2:179631129;179631128;179631127 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs371249764  |
-0.583 | 0.999 | N | 0.541 | 0.22 | None | gnomAD-2.1.1 | 1.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.76E-05 | 1.63239E-04 |
| S/C | rs371249764 |
-0.583 | 0.999 | N | 0.541 | 0.22 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| S/C | rs371249764 |
-0.583 | 0.999 | N | 0.541 | 0.22 | None | gnomAD-4.0.0 | 1.54964E-05 | None | None | None | None | N | None | 0 | 1.667E-05 | None | 0 | 0 | None | 0 | 0 | 2.03495E-05 | 0 | 0 |
| S/F | None | None | 0.988 | N | 0.597 | 0.196 | 0.33085137897 | gnomAD-4.0.0 | 1.36882E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15955E-05 | 1.6564E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1123 | likely_benign | 0.1055 | benign | -0.733 | Destabilizing | 0.826 | D | 0.362 | neutral | N | 0.385774891 | None | None | N |
| S/C | 0.2365 | likely_benign | 0.1845 | benign | -0.444 | Destabilizing | 0.999 | D | 0.541 | neutral | N | 0.388468326 | None | None | N |
| S/D | 0.8324 | likely_pathogenic | 0.8239 | pathogenic | 0.391 | Stabilizing | 0.884 | D | 0.514 | neutral | None | None | None | None | N |
| S/E | 0.8416 | likely_pathogenic | 0.8281 | pathogenic | 0.346 | Stabilizing | 0.17 | N | 0.241 | neutral | None | None | None | None | N |
| S/F | 0.4796 | ambiguous | 0.4514 | ambiguous | -1.094 | Destabilizing | 0.988 | D | 0.597 | neutral | N | 0.354044989 | None | None | N |
| S/G | 0.2403 | likely_benign | 0.2171 | benign | -0.914 | Destabilizing | 0.969 | D | 0.517 | neutral | None | None | None | None | N |
| S/H | 0.6308 | likely_pathogenic | 0.5798 | pathogenic | -1.328 | Destabilizing | 0.997 | D | 0.553 | neutral | None | None | None | None | N |
| S/I | 0.3859 | ambiguous | 0.341 | ambiguous | -0.368 | Destabilizing | 0.17 | N | 0.431 | neutral | None | None | None | None | N |
| S/K | 0.8719 | likely_pathogenic | 0.8448 | pathogenic | -0.434 | Destabilizing | 0.939 | D | 0.507 | neutral | None | None | None | None | N |
| S/L | 0.2378 | likely_benign | 0.2262 | benign | -0.368 | Destabilizing | 0.759 | D | 0.455 | neutral | None | None | None | None | N |
| S/M | 0.3909 | ambiguous | 0.3492 | ambiguous | -0.1 | Destabilizing | 0.991 | D | 0.557 | neutral | None | None | None | None | N |
| S/N | 0.38 | ambiguous | 0.3434 | ambiguous | -0.25 | Destabilizing | 0.969 | D | 0.511 | neutral | None | None | None | None | N |
| S/P | 0.8836 | likely_pathogenic | 0.8509 | pathogenic | -0.458 | Destabilizing | 0.996 | D | 0.572 | neutral | N | 0.387478034 | None | None | N |
| S/Q | 0.7433 | likely_pathogenic | 0.7065 | pathogenic | -0.465 | Destabilizing | 0.982 | D | 0.545 | neutral | None | None | None | None | N |
| S/R | 0.7878 | likely_pathogenic | 0.7492 | pathogenic | -0.295 | Destabilizing | 0.982 | D | 0.572 | neutral | None | None | None | None | N |
| S/T | 0.1075 | likely_benign | 0.0969 | benign | -0.415 | Destabilizing | 0.134 | N | 0.23 | neutral | N | 0.356870338 | None | None | N |
| S/V | 0.3138 | likely_benign | 0.262 | benign | -0.458 | Destabilizing | 0.759 | D | 0.454 | neutral | None | None | None | None | N |
| S/W | 0.7167 | likely_pathogenic | 0.6857 | pathogenic | -0.999 | Destabilizing | 0.999 | D | 0.658 | neutral | None | None | None | None | N |
| S/Y | 0.4716 | ambiguous | 0.4416 | ambiguous | -0.75 | Destabilizing | 0.996 | D | 0.601 | neutral | N | 0.333225877 | 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.