Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30288 | 91087;91088;91089 | chr2:178552038;178552037;178552036 | chr2:179416765;179416764;179416763 |
| N2AB | 28647 | 86164;86165;86166 | chr2:178552038;178552037;178552036 | chr2:179416765;179416764;179416763 |
| N2A | 27720 | 83383;83384;83385 | chr2:178552038;178552037;178552036 | chr2:179416765;179416764;179416763 |
| N2B | 21223 | 63892;63893;63894 | chr2:178552038;178552037;178552036 | chr2:179416765;179416764;179416763 |
| Novex-1 | 21348 | 64267;64268;64269 | chr2:178552038;178552037;178552036 | chr2:179416765;179416764;179416763 |
| Novex-2 | 21415 | 64468;64469;64470 | chr2:178552038;178552037;178552036 | chr2:179416765;179416764;179416763 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/T | rs763525672  |
0.282 | 0.999 | N | 0.683 | 0.551 | 0.500303608228 | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.11E-05 | 0 |
| N/T | rs763525672 |
0.282 | 0.999 | N | 0.683 | 0.551 | 0.500303608228 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| N/T | rs763525672 |
0.282 | 0.999 | N | 0.683 | 0.551 | 0.500303608228 | gnomAD-4.0.0 | 1.0536E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.35626E-05 | 0 | 1.60138E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.3024 | likely_benign | 0.2413 | benign | -0.178 | Destabilizing | 1.0 | D | 0.634 | neutral | None | None | None | None | I |
| N/C | 0.267 | likely_benign | 0.2439 | benign | 0.326 | Stabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | I |
| N/D | 0.4368 | ambiguous | 0.267 | benign | 0.148 | Stabilizing | 0.999 | D | 0.611 | neutral | N | 0.437748504 | None | None | I |
| N/E | 0.787 | likely_pathogenic | 0.6193 | pathogenic | 0.105 | Stabilizing | 0.999 | D | 0.683 | prob.neutral | None | None | None | None | I |
| N/F | 0.6272 | likely_pathogenic | 0.5391 | ambiguous | -0.636 | Destabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | I |
| N/G | 0.2742 | likely_benign | 0.2253 | benign | -0.325 | Destabilizing | 0.999 | D | 0.527 | neutral | None | None | None | None | I |
| N/H | 0.1185 | likely_benign | 0.1026 | benign | -0.339 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | N | 0.471132203 | None | None | I |
| N/I | 0.4805 | ambiguous | 0.3747 | ambiguous | 0.116 | Stabilizing | 1.0 | D | 0.67 | neutral | N | 0.48456565 | None | None | I |
| N/K | 0.6163 | likely_pathogenic | 0.4342 | ambiguous | 0.127 | Stabilizing | 1.0 | D | 0.699 | prob.neutral | N | 0.433710908 | None | None | I |
| N/L | 0.3513 | ambiguous | 0.29 | benign | 0.116 | Stabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | I |
| N/M | 0.4877 | ambiguous | 0.3978 | ambiguous | 0.288 | Stabilizing | 1.0 | D | 0.64 | neutral | None | None | None | None | I |
| N/P | 0.8304 | likely_pathogenic | 0.7913 | pathogenic | 0.044 | Stabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | I |
| N/Q | 0.4976 | ambiguous | 0.3969 | ambiguous | -0.234 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | I |
| N/R | 0.5728 | likely_pathogenic | 0.4429 | ambiguous | 0.184 | Stabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | I |
| N/S | 0.0993 | likely_benign | 0.0942 | benign | -0.026 | Destabilizing | 0.999 | D | 0.551 | neutral | N | 0.517654869 | None | None | I |
| N/T | 0.272 | likely_benign | 0.2061 | benign | 0.062 | Stabilizing | 0.999 | D | 0.683 | prob.neutral | N | 0.487185769 | None | None | I |
| N/V | 0.3844 | ambiguous | 0.318 | benign | 0.044 | Stabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | I |
| N/W | 0.8494 | likely_pathogenic | 0.7935 | pathogenic | -0.698 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | I |
| N/Y | 0.211 | likely_benign | 0.1686 | benign | -0.399 | Destabilizing | 1.0 | D | 0.653 | neutral | N | 0.49583305 | 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.