Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21328 | 64207;64208;64209 | chr2:178587229;178587228;178587227 | chr2:179451956;179451955;179451954 |
| N2AB | 19687 | 59284;59285;59286 | chr2:178587229;178587228;178587227 | chr2:179451956;179451955;179451954 |
| N2A | 18760 | 56503;56504;56505 | chr2:178587229;178587228;178587227 | chr2:179451956;179451955;179451954 |
| N2B | 12263 | 37012;37013;37014 | chr2:178587229;178587228;178587227 | chr2:179451956;179451955;179451954 |
| Novex-1 | 12388 | 37387;37388;37389 | chr2:178587229;178587228;178587227 | chr2:179451956;179451955;179451954 |
| Novex-2 | 12455 | 37588;37589;37590 | chr2:178587229;178587228;178587227 | chr2:179451956;179451955;179451954 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/N | rs370506995  |
None | 0.188 | N | 0.49 | 0.139 | 0.321672782286 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/N | rs370506995 |
None | 0.188 | N | 0.49 | 0.139 | 0.321672782286 | gnomAD-4.0.0 | 2.56422E-06 | None | None | None | None | N | None | 0 | 1.69635E-05 | None | 0 | 0 | None | 0 | 0 | 2.39485E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0657 | likely_benign | 0.073 | benign | -0.775 | Destabilizing | None | N | 0.188 | neutral | N | 0.471372466 | None | None | N |
| T/C | 0.2853 | likely_benign | 0.3157 | benign | -0.375 | Destabilizing | 0.824 | D | 0.619 | neutral | None | None | None | None | N |
| T/D | 0.3009 | likely_benign | 0.3544 | ambiguous | -0.007 | Destabilizing | 0.081 | N | 0.558 | neutral | None | None | None | None | N |
| T/E | 0.2558 | likely_benign | 0.2986 | benign | -0.029 | Destabilizing | 0.081 | N | 0.532 | neutral | None | None | None | None | N |
| T/F | 0.2217 | likely_benign | 0.2514 | benign | -0.977 | Destabilizing | 0.555 | D | 0.687 | prob.neutral | None | None | None | None | N |
| T/G | 0.1295 | likely_benign | 0.1414 | benign | -1.002 | Destabilizing | 0.081 | N | 0.546 | neutral | None | None | None | None | N |
| T/H | 0.2083 | likely_benign | 0.2296 | benign | -1.248 | Destabilizing | 0.824 | D | 0.675 | neutral | None | None | None | None | N |
| T/I | 0.1354 | likely_benign | 0.1591 | benign | -0.269 | Destabilizing | 0.317 | N | 0.596 | neutral | N | 0.471487824 | None | None | N |
| T/K | 0.1754 | likely_benign | 0.2002 | benign | -0.636 | Destabilizing | 0.081 | N | 0.535 | neutral | None | None | None | None | N |
| T/L | 0.0783 | likely_benign | 0.0838 | benign | -0.269 | Destabilizing | 0.149 | N | 0.486 | neutral | None | None | None | None | N |
| T/M | 0.0838 | likely_benign | 0.0924 | benign | 0.046 | Stabilizing | 0.935 | D | 0.623 | neutral | None | None | None | None | N |
| T/N | 0.0865 | likely_benign | 0.0993 | benign | -0.494 | Destabilizing | 0.188 | N | 0.49 | neutral | N | 0.515673357 | None | None | N |
| T/P | 0.0698 | likely_benign | 0.0761 | benign | -0.406 | Destabilizing | None | N | 0.321 | neutral | D | 0.52383148 | None | None | N |
| T/Q | 0.1738 | likely_benign | 0.1926 | benign | -0.669 | Destabilizing | 0.38 | N | 0.642 | neutral | None | None | None | None | N |
| T/R | 0.1844 | likely_benign | 0.1949 | benign | -0.368 | Destabilizing | 0.38 | N | 0.623 | neutral | None | None | None | None | N |
| T/S | 0.0783 | likely_benign | 0.0845 | benign | -0.787 | Destabilizing | None | N | 0.296 | neutral | N | 0.450621801 | None | None | N |
| T/V | 0.1043 | likely_benign | 0.1152 | benign | -0.406 | Destabilizing | 0.081 | N | 0.417 | neutral | None | None | None | None | N |
| T/W | 0.5151 | ambiguous | 0.5508 | ambiguous | -0.913 | Destabilizing | 0.935 | D | 0.699 | prob.neutral | None | None | None | None | N |
| T/Y | 0.2349 | likely_benign | 0.2664 | benign | -0.683 | Destabilizing | 0.555 | D | 0.69 | prob.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.