Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19825 | 59698;59699;59700 | chr2:178592532;178592531;178592530 | chr2:179457259;179457258;179457257 |
| N2AB | 18184 | 54775;54776;54777 | chr2:178592532;178592531;178592530 | chr2:179457259;179457258;179457257 |
| N2A | 17257 | 51994;51995;51996 | chr2:178592532;178592531;178592530 | chr2:179457259;179457258;179457257 |
| N2B | 10760 | 32503;32504;32505 | chr2:178592532;178592531;178592530 | chr2:179457259;179457258;179457257 |
| Novex-1 | 10885 | 32878;32879;32880 | chr2:178592532;178592531;178592530 | chr2:179457259;179457258;179457257 |
| Novex-2 | 10952 | 33079;33080;33081 | chr2:178592532;178592531;178592530 | chr2:179457259;179457258;179457257 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/T | rs376465623  |
0.266 | 0.081 | N | 0.309 | 0.103 | None | gnomAD-2.1.1 | 6.08E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 4E-05 | 1.09598E-04 | 1.40568E-04 |
| R/T | rs376465623 |
0.266 | 0.081 | N | 0.309 | 0.103 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.36E-05 | 0 | 0 |
| R/T | rs376465623 |
0.266 | 0.081 | N | 0.309 | 0.103 | None | gnomAD-4.0.0 | 1.02269E-04 | None | None | None | None | N | None | 5.34102E-05 | 0 | None | 0 | 0 | None | 3.12402E-05 | 0 | 1.2801E-04 | 0 | 1.28115E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.1711 | likely_benign | 0.1455 | benign | 0.032 | Stabilizing | 0.001 | N | 0.167 | neutral | None | None | None | None | N |
| R/C | 0.117 | likely_benign | 0.1094 | benign | 0.07 | Stabilizing | 0.958 | D | 0.237 | neutral | None | None | None | None | N |
| R/D | 0.3138 | likely_benign | 0.2707 | benign | 0.06 | Stabilizing | 0.22 | N | 0.344 | neutral | None | None | None | None | N |
| R/E | 0.1793 | likely_benign | 0.1528 | benign | 0.14 | Stabilizing | 0.055 | N | 0.211 | neutral | None | None | None | None | N |
| R/F | 0.329 | likely_benign | 0.2734 | benign | -0.067 | Destabilizing | 0.667 | D | 0.309 | neutral | None | None | None | None | N |
| R/G | 0.1022 | likely_benign | 0.0875 | benign | -0.207 | Destabilizing | 0.042 | N | 0.263 | neutral | N | 0.420408829 | None | None | N |
| R/H | 0.0758 | likely_benign | 0.0728 | benign | -0.748 | Destabilizing | 0.001 | N | 0.24 | neutral | None | None | None | None | N |
| R/I | 0.1483 | likely_benign | 0.1247 | benign | 0.635 | Stabilizing | 0.301 | N | 0.345 | neutral | N | 0.493405078 | None | None | N |
| R/K | 0.0738 | likely_benign | 0.0638 | benign | 0.052 | Stabilizing | None | N | 0.151 | neutral | N | 0.428852167 | None | None | N |
| R/L | 0.1481 | likely_benign | 0.1309 | benign | 0.635 | Stabilizing | 0.104 | N | 0.314 | neutral | None | None | None | None | N |
| R/M | 0.153 | likely_benign | 0.1333 | benign | 0.207 | Stabilizing | 0.859 | D | 0.268 | neutral | None | None | None | None | N |
| R/N | 0.2626 | likely_benign | 0.2143 | benign | 0.42 | Stabilizing | 0.22 | N | 0.227 | neutral | None | None | None | None | N |
| R/P | 0.6248 | likely_pathogenic | 0.6764 | pathogenic | 0.456 | Stabilizing | 0.364 | N | 0.379 | neutral | None | None | None | None | N |
| R/Q | 0.0749 | likely_benign | 0.0686 | benign | 0.296 | Stabilizing | 0.124 | N | 0.283 | neutral | None | None | None | None | N |
| R/S | 0.2029 | likely_benign | 0.1701 | benign | 0.007 | Stabilizing | 0.042 | N | 0.281 | neutral | N | 0.471352151 | None | None | N |
| R/T | 0.1059 | likely_benign | 0.0927 | benign | 0.236 | Stabilizing | 0.081 | N | 0.309 | neutral | N | 0.48678575 | None | None | N |
| R/V | 0.1771 | likely_benign | 0.152 | benign | 0.456 | Stabilizing | 0.104 | N | 0.332 | neutral | None | None | None | None | N |
| R/W | 0.1314 | likely_benign | 0.1388 | benign | -0.047 | Destabilizing | 0.958 | D | 0.237 | neutral | None | None | None | None | N |
| R/Y | 0.2486 | likely_benign | 0.2131 | benign | 0.348 | Stabilizing | 0.22 | N | 0.345 | 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.