Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30960 | 93103;93104;93105 | chr2:178548748;178548747;178548746 | chr2:179413475;179413474;179413473 |
| N2AB | 29319 | 88180;88181;88182 | chr2:178548748;178548747;178548746 | chr2:179413475;179413474;179413473 |
| N2A | 28392 | 85399;85400;85401 | chr2:178548748;178548747;178548746 | chr2:179413475;179413474;179413473 |
| N2B | 21895 | 65908;65909;65910 | chr2:178548748;178548747;178548746 | chr2:179413475;179413474;179413473 |
| Novex-1 | 22020 | 66283;66284;66285 | chr2:178548748;178548747;178548746 | chr2:179413475;179413474;179413473 |
| Novex-2 | 22087 | 66484;66485;66486 | chr2:178548748;178548747;178548746 | chr2:179413475;179413474;179413473 |
| 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/N | rs373494929  |
-0.57 | 0.334 | N | 0.588 | 0.147 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| S/R | rs968631165 |
-0.192 | 0.638 | N | 0.728 | 0.121 | 0.195762928549 | gnomAD-2.1.1 | 7.14E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.56E-05 | 0 |
| S/R | rs968631165 |
-0.192 | 0.638 | N | 0.728 | 0.121 | 0.195762928549 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| S/R | rs968631165 |
-0.192 | 0.638 | N | 0.728 | 0.121 | 0.195762928549 | gnomAD-4.0.0 | 9.29632E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.27139E-05 | 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 | 0.0878 | likely_benign | 0.0936 | benign | -0.733 | Destabilizing | 0.121 | N | 0.475 | neutral | None | None | None | None | N |
| S/C | 0.0879 | likely_benign | 0.0987 | benign | -0.362 | Destabilizing | 0.931 | D | 0.707 | prob.neutral | N | 0.463009495 | None | None | N |
| S/D | 0.36 | ambiguous | 0.3829 | ambiguous | 0.321 | Stabilizing | 0.399 | N | 0.607 | neutral | None | None | None | None | N |
| S/E | 0.3751 | ambiguous | 0.3862 | ambiguous | 0.373 | Stabilizing | 0.399 | N | 0.603 | neutral | None | None | None | None | N |
| S/F | 0.1739 | likely_benign | 0.1929 | benign | -0.957 | Destabilizing | 0.826 | D | 0.745 | deleterious | None | None | None | None | N |
| S/G | 0.0941 | likely_benign | 0.0966 | benign | -1.01 | Destabilizing | 0.334 | N | 0.545 | neutral | N | 0.457983065 | None | None | N |
| S/H | 0.2165 | likely_benign | 0.2319 | benign | -1.321 | Destabilizing | 0.982 | D | 0.71 | prob.delet. | None | None | None | None | N |
| S/I | 0.1518 | likely_benign | 0.1582 | benign | -0.088 | Destabilizing | 0.468 | N | 0.713 | prob.delet. | N | 0.506519864 | None | None | N |
| S/K | 0.3963 | ambiguous | 0.4424 | ambiguous | -0.124 | Destabilizing | 0.399 | N | 0.603 | neutral | None | None | None | None | N |
| S/L | 0.0872 | likely_benign | 0.0959 | benign | -0.088 | Destabilizing | 0.25 | N | 0.628 | neutral | None | None | None | None | N |
| S/M | 0.1272 | likely_benign | 0.1464 | benign | -0.061 | Destabilizing | 0.947 | D | 0.713 | prob.delet. | None | None | None | None | N |
| S/N | 0.0936 | likely_benign | 0.1056 | benign | -0.282 | Destabilizing | 0.334 | N | 0.588 | neutral | N | 0.457983065 | None | None | N |
| S/P | 0.9359 | likely_pathogenic | 0.9519 | pathogenic | -0.269 | Destabilizing | 0.826 | D | 0.721 | prob.delet. | None | None | None | None | N |
| S/Q | 0.2991 | likely_benign | 0.3201 | benign | -0.266 | Destabilizing | 0.826 | D | 0.691 | prob.neutral | None | None | None | None | N |
| S/R | 0.3537 | ambiguous | 0.4001 | ambiguous | -0.211 | Destabilizing | 0.638 | D | 0.728 | prob.delet. | N | 0.479661337 | None | None | N |
| S/T | 0.0641 | likely_benign | 0.0721 | benign | -0.303 | Destabilizing | 0.001 | N | 0.293 | neutral | N | 0.419804957 | None | None | N |
| S/V | 0.1484 | likely_benign | 0.1622 | benign | -0.269 | Destabilizing | 0.25 | N | 0.643 | neutral | None | None | None | None | N |
| S/W | 0.3077 | likely_benign | 0.327 | benign | -0.961 | Destabilizing | 0.982 | D | 0.733 | prob.delet. | None | None | None | None | N |
| S/Y | 0.1687 | likely_benign | 0.1796 | benign | -0.62 | Destabilizing | 0.826 | D | 0.74 | deleterious | 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.