Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19730 | 59413;59414;59415 | chr2:178592931;178592930;178592929 | chr2:179457658;179457657;179457656 |
| N2AB | 18089 | 54490;54491;54492 | chr2:178592931;178592930;178592929 | chr2:179457658;179457657;179457656 |
| N2A | 17162 | 51709;51710;51711 | chr2:178592931;178592930;178592929 | chr2:179457658;179457657;179457656 |
| N2B | 10665 | 32218;32219;32220 | chr2:178592931;178592930;178592929 | chr2:179457658;179457657;179457656 |
| Novex-1 | 10790 | 32593;32594;32595 | chr2:178592931;178592930;178592929 | chr2:179457658;179457657;179457656 |
| Novex-2 | 10857 | 32794;32795;32796 | chr2:178592931;178592930;178592929 | chr2:179457658;179457657;179457656 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/D | rs1471424037  |
-1.545 | 0.982 | N | 0.717 | 0.354 | 0.606623169391 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| A/D | rs1471424037 |
-1.545 | 0.982 | N | 0.717 | 0.354 | 0.606623169391 | gnomAD-4.0.0 | 1.59175E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77377E-05 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs2050547088 |
None | 0.885 | N | 0.567 | 0.158 | 0.288352970974 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 0 |
| A/V | rs1471424037 |
None | 0.17 | N | 0.375 | 0.241 | 0.288727942641 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.94553E-04 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs1471424037 |
None | 0.17 | N | 0.375 | 0.241 | 0.288727942641 | gnomAD-4.0.0 | 3.8454E-06 | None | None | None | None | N | None | 0 | 1.6956E-05 | None | 0 | 2.42766E-05 | None | 0 | 0 | 0 | 1.3403E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5274 | ambiguous | 0.492 | ambiguous | -0.462 | Destabilizing | 0.999 | D | 0.689 | prob.neutral | None | None | None | None | N |
| A/D | 0.9005 | likely_pathogenic | 0.8184 | pathogenic | -1.399 | Destabilizing | 0.982 | D | 0.717 | prob.delet. | N | 0.480825759 | None | None | N |
| A/E | 0.8794 | likely_pathogenic | 0.7744 | pathogenic | -1.317 | Destabilizing | 0.986 | D | 0.69 | prob.neutral | None | None | None | None | N |
| A/F | 0.8305 | likely_pathogenic | 0.7364 | pathogenic | -0.754 | Destabilizing | 0.993 | D | 0.737 | prob.delet. | None | None | None | None | N |
| A/G | 0.2369 | likely_benign | 0.2584 | benign | -1.197 | Destabilizing | 0.885 | D | 0.521 | neutral | N | 0.474331299 | None | None | N |
| A/H | 0.9397 | likely_pathogenic | 0.8941 | pathogenic | -1.596 | Destabilizing | 0.999 | D | 0.717 | prob.delet. | None | None | None | None | N |
| A/I | 0.5049 | ambiguous | 0.3931 | ambiguous | 0.06 | Stabilizing | 0.91 | D | 0.619 | neutral | None | None | None | None | N |
| A/K | 0.9601 | likely_pathogenic | 0.915 | pathogenic | -1.048 | Destabilizing | 0.986 | D | 0.693 | prob.neutral | None | None | None | None | N |
| A/L | 0.6109 | likely_pathogenic | 0.5075 | ambiguous | 0.06 | Stabilizing | 0.91 | D | 0.529 | neutral | None | None | None | None | N |
| A/M | 0.6514 | likely_pathogenic | 0.5359 | ambiguous | 0.153 | Stabilizing | 0.998 | D | 0.712 | prob.delet. | None | None | None | None | N |
| A/N | 0.8483 | likely_pathogenic | 0.7675 | pathogenic | -0.915 | Destabilizing | 0.986 | D | 0.712 | prob.delet. | None | None | None | None | N |
| A/P | 0.8438 | likely_pathogenic | 0.8521 | pathogenic | -0.195 | Destabilizing | 0.991 | D | 0.722 | prob.delet. | N | 0.475091768 | None | None | N |
| A/Q | 0.8858 | likely_pathogenic | 0.812 | pathogenic | -0.9 | Destabilizing | 0.993 | D | 0.733 | prob.delet. | None | None | None | None | N |
| A/R | 0.9407 | likely_pathogenic | 0.8814 | pathogenic | -0.949 | Destabilizing | 0.986 | D | 0.737 | prob.delet. | None | None | None | None | N |
| A/S | 0.2161 | likely_benign | 0.1952 | benign | -1.282 | Destabilizing | 0.322 | N | 0.421 | neutral | N | 0.468708985 | None | None | N |
| A/T | 0.2976 | likely_benign | 0.2123 | benign | -1.094 | Destabilizing | 0.885 | D | 0.567 | neutral | N | 0.510534109 | None | None | N |
| A/V | 0.2429 | likely_benign | 0.1756 | benign | -0.195 | Destabilizing | 0.17 | N | 0.375 | neutral | N | 0.399422189 | None | None | N |
| A/W | 0.9743 | likely_pathogenic | 0.952 | pathogenic | -1.366 | Destabilizing | 0.999 | D | 0.711 | prob.delet. | None | None | None | None | N |
| A/Y | 0.9167 | likely_pathogenic | 0.8566 | pathogenic | -0.825 | Destabilizing | 0.998 | D | 0.734 | prob.delet. | 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.