Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32630 | 98113;98114;98115 | chr2:178540278;178540277;178540276 | chr2:179405005;179405004;179405003 |
| N2AB | 30989 | 93190;93191;93192 | chr2:178540278;178540277;178540276 | chr2:179405005;179405004;179405003 |
| N2A | 30062 | 90409;90410;90411 | chr2:178540278;178540277;178540276 | chr2:179405005;179405004;179405003 |
| N2B | 23565 | 70918;70919;70920 | chr2:178540278;178540277;178540276 | chr2:179405005;179405004;179405003 |
| Novex-1 | 23690 | 71293;71294;71295 | chr2:178540278;178540277;178540276 | chr2:179405005;179405004;179405003 |
| Novex-2 | 23757 | 71494;71495;71496 | chr2:178540278;178540277;178540276 | chr2:179405005;179405004;179405003 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | rs1553512070  |
None | 0.198 | N | 0.373 | 0.085 | 0.158396225186 | gnomAD-4.0.0 | 3.18243E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85829E-06 | 0 | 3.02425E-05 |
| S/F | None | None | 0.999 | N | 0.705 | 0.422 | 0.638795284799 | gnomAD-4.0.0 | 6.84202E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15931E-05 | 0 |
| S/P | rs1553512070 |
None | 0.997 | N | 0.623 | 0.418 | 0.336892272479 | gnomAD-4.0.0 | 1.59122E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85829E-06 | 0 | 0 |
| S/Y | None | None | 0.999 | D | 0.701 | 0.462 | 0.652253901461 | gnomAD-4.0.0 | 1.3684E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79895E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0947 | likely_benign | 0.1018 | benign | -0.484 | Destabilizing | 0.198 | N | 0.373 | neutral | N | 0.446754776 | None | None | I |
| S/C | 0.0986 | likely_benign | 0.1049 | benign | -0.278 | Destabilizing | 1.0 | D | 0.621 | neutral | N | 0.521292607 | None | None | I |
| S/D | 0.7344 | likely_pathogenic | 0.8153 | pathogenic | -0.315 | Destabilizing | 0.998 | D | 0.68 | prob.neutral | None | None | None | None | I |
| S/E | 0.7679 | likely_pathogenic | 0.8311 | pathogenic | -0.399 | Destabilizing | 0.992 | D | 0.675 | neutral | None | None | None | None | I |
| S/F | 0.3558 | ambiguous | 0.4363 | ambiguous | -1.031 | Destabilizing | 0.999 | D | 0.705 | prob.neutral | N | 0.509240044 | None | None | I |
| S/G | 0.1306 | likely_benign | 0.1363 | benign | -0.617 | Destabilizing | 0.923 | D | 0.595 | neutral | None | None | None | None | I |
| S/H | 0.5562 | ambiguous | 0.622 | pathogenic | -1.191 | Destabilizing | 1.0 | D | 0.619 | neutral | None | None | None | None | I |
| S/I | 0.441 | ambiguous | 0.5476 | ambiguous | -0.256 | Destabilizing | 0.998 | D | 0.7 | prob.neutral | None | None | None | None | I |
| S/K | 0.882 | likely_pathogenic | 0.932 | pathogenic | -0.568 | Destabilizing | 0.983 | D | 0.681 | prob.neutral | None | None | None | None | I |
| S/L | 0.1658 | likely_benign | 0.2115 | benign | -0.256 | Destabilizing | 0.983 | D | 0.657 | neutral | None | None | None | None | I |
| S/M | 0.2927 | likely_benign | 0.3423 | ambiguous | 0.211 | Stabilizing | 1.0 | D | 0.62 | neutral | None | None | None | None | I |
| S/N | 0.3478 | ambiguous | 0.4014 | ambiguous | -0.326 | Destabilizing | 0.999 | D | 0.69 | prob.neutral | None | None | None | None | I |
| S/P | 0.935 | likely_pathogenic | 0.9616 | pathogenic | -0.303 | Destabilizing | 0.997 | D | 0.623 | neutral | N | 0.497630249 | None | None | I |
| S/Q | 0.6586 | likely_pathogenic | 0.7098 | pathogenic | -0.668 | Destabilizing | 0.999 | D | 0.664 | neutral | None | None | None | None | I |
| S/R | 0.828 | likely_pathogenic | 0.8896 | pathogenic | -0.298 | Destabilizing | 0.998 | D | 0.619 | neutral | None | None | None | None | I |
| S/T | 0.2036 | likely_benign | 0.2368 | benign | -0.405 | Destabilizing | 0.978 | D | 0.61 | neutral | N | 0.513518486 | None | None | I |
| S/V | 0.368 | ambiguous | 0.4457 | ambiguous | -0.303 | Destabilizing | 0.983 | D | 0.663 | neutral | None | None | None | None | I |
| S/W | 0.531 | ambiguous | 0.6056 | pathogenic | -0.995 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | I |
| S/Y | 0.3313 | likely_benign | 0.4039 | ambiguous | -0.728 | Destabilizing | 0.999 | D | 0.701 | prob.neutral | D | 0.527090809 | 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.