Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2191 | 6796;6797;6798 | chr2:178775140;178775139;178775138 | chr2:179639867;179639866;179639865 |
| N2AB | 2191 | 6796;6797;6798 | chr2:178775140;178775139;178775138 | chr2:179639867;179639866;179639865 |
| N2A | 2191 | 6796;6797;6798 | chr2:178775140;178775139;178775138 | chr2:179639867;179639866;179639865 |
| N2B | 2145 | 6658;6659;6660 | chr2:178775140;178775139;178775138 | chr2:179639867;179639866;179639865 |
| Novex-1 | 2145 | 6658;6659;6660 | chr2:178775140;178775139;178775138 | chr2:179639867;179639866;179639865 |
| Novex-2 | 2145 | 6658;6659;6660 | chr2:178775140;178775139;178775138 | chr2:179639867;179639866;179639865 |
| Novex-3 | 2191 | 6796;6797;6798 | chr2:178775140;178775139;178775138 | chr2:179639867;179639866;179639865 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/V | rs760003993  |
-0.008 | 0.45 | N | 0.408 | 0.341 | 0.418221603839 | gnomAD-2.1.1 | 1.2E-05 | None | None | None | None | N | None | 6.15E-05 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.84E-06 | 0 |
| M/V | rs760003993 |
-0.008 | 0.45 | N | 0.408 | 0.341 | 0.418221603839 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 0 |
| M/V | rs760003993 |
-0.008 | 0.45 | N | 0.408 | 0.341 | 0.418221603839 | gnomAD-4.0.0 | 4.33728E-06 | None | None | None | None | N | None | 1.33494E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.38986E-06 | 1.09791E-05 | 1.60041E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.6634 | likely_pathogenic | 0.6402 | pathogenic | -0.559 | Destabilizing | 0.91 | D | 0.507 | neutral | None | None | None | None | N |
| M/C | 0.9184 | likely_pathogenic | 0.9079 | pathogenic | -0.553 | Destabilizing | 0.999 | D | 0.567 | neutral | None | None | None | None | N |
| M/D | 0.9649 | likely_pathogenic | 0.9604 | pathogenic | 0.529 | Stabilizing | 0.996 | D | 0.659 | neutral | None | None | None | None | N |
| M/E | 0.8028 | likely_pathogenic | 0.7952 | pathogenic | 0.498 | Stabilizing | 0.996 | D | 0.63 | neutral | None | None | None | None | N |
| M/F | 0.6008 | likely_pathogenic | 0.5984 | pathogenic | -0.058 | Destabilizing | 0.961 | D | 0.455 | neutral | None | None | None | None | N |
| M/G | 0.9062 | likely_pathogenic | 0.8925 | pathogenic | -0.777 | Destabilizing | 0.996 | D | 0.66 | neutral | None | None | None | None | N |
| M/H | 0.8259 | likely_pathogenic | 0.8121 | pathogenic | 0.042 | Stabilizing | 0.999 | D | 0.649 | neutral | None | None | None | None | N |
| M/I | 0.6306 | likely_pathogenic | 0.6169 | pathogenic | -0.068 | Destabilizing | 0.108 | N | 0.299 | neutral | N | 0.499180051 | None | None | N |
| M/K | 0.5293 | ambiguous | 0.5156 | ambiguous | 0.464 | Stabilizing | 0.982 | D | 0.55 | neutral | N | 0.467591185 | None | None | N |
| M/L | 0.2687 | likely_benign | 0.2606 | benign | -0.068 | Destabilizing | 0.261 | N | 0.321 | neutral | N | 0.482762688 | None | None | N |
| M/N | 0.8359 | likely_pathogenic | 0.8191 | pathogenic | 0.581 | Stabilizing | 0.996 | D | 0.636 | neutral | None | None | None | None | N |
| M/P | 0.975 | likely_pathogenic | 0.9715 | pathogenic | -0.201 | Destabilizing | 0.996 | D | 0.631 | neutral | None | None | None | None | N |
| M/Q | 0.5412 | ambiguous | 0.5325 | ambiguous | 0.454 | Stabilizing | 0.996 | D | 0.436 | neutral | None | None | None | None | N |
| M/R | 0.5785 | likely_pathogenic | 0.5624 | ambiguous | 0.872 | Stabilizing | 0.995 | D | 0.545 | neutral | N | 0.4678303 | None | None | N |
| M/S | 0.697 | likely_pathogenic | 0.6739 | pathogenic | 0.034 | Stabilizing | 0.987 | D | 0.521 | neutral | None | None | None | None | N |
| M/T | 0.4548 | ambiguous | 0.4267 | ambiguous | 0.115 | Stabilizing | 0.948 | D | 0.509 | neutral | N | 0.440488371 | None | None | N |
| M/V | 0.1415 | likely_benign | 0.1334 | benign | -0.201 | Destabilizing | 0.45 | N | 0.408 | neutral | N | 0.494553346 | None | None | N |
| M/W | 0.9003 | likely_pathogenic | 0.8926 | pathogenic | -0.035 | Destabilizing | 0.999 | D | 0.573 | neutral | None | None | None | None | N |
| M/Y | 0.8386 | likely_pathogenic | 0.8276 | pathogenic | 0.113 | Stabilizing | 0.996 | D | 0.551 | 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.