Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3017 | 9274;9275;9276 | chr2:178768787;178768786;178768785 | chr2:179633514;179633513;179633512 |
| N2AB | 3017 | 9274;9275;9276 | chr2:178768787;178768786;178768785 | chr2:179633514;179633513;179633512 |
| N2A | 3017 | 9274;9275;9276 | chr2:178768787;178768786;178768785 | chr2:179633514;179633513;179633512 |
| N2B | 2971 | 9136;9137;9138 | chr2:178768787;178768786;178768785 | chr2:179633514;179633513;179633512 |
| Novex-1 | 2971 | 9136;9137;9138 | chr2:178768787;178768786;178768785 | chr2:179633514;179633513;179633512 |
| Novex-2 | 2971 | 9136;9137;9138 | chr2:178768787;178768786;178768785 | chr2:179633514;179633513;179633512 |
| Novex-3 | 3017 | 9274;9275;9276 | chr2:178768787;178768786;178768785 | chr2:179633514;179633513;179633512 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/I | rs372303620  |
None | 0.991 | N | 0.733 | 0.596 | 0.774813597514 | gnomAD-4.0.0 | 1.36817E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52131E-05 | None | 0 | 0 | 8.99294E-07 | 0 | 0 |
| R/K | rs372303620 |
0.21 | 0.046 | N | 0.208 | 0.22 | None | gnomAD-2.1.1 | 1.77E-05 | None | None | None | None | N | None | 2.00337E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/K | rs372303620 |
0.21 | 0.046 | N | 0.208 | 0.22 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 9.66E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/K | rs372303620 |
0.21 | 0.046 | N | 0.208 | 0.22 | None | gnomAD-4.0.0 | 8.05506E-06 | None | None | None | None | N | None | 1.46866E-04 | 1.66728E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60061E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8409 | likely_pathogenic | 0.9073 | pathogenic | -0.283 | Destabilizing | 0.953 | D | 0.596 | neutral | None | None | None | None | N |
| R/C | 0.5174 | ambiguous | 0.6456 | pathogenic | -0.254 | Destabilizing | 0.999 | D | 0.689 | prob.neutral | None | None | None | None | N |
| R/D | 0.938 | likely_pathogenic | 0.9665 | pathogenic | -0.072 | Destabilizing | 0.986 | D | 0.709 | prob.delet. | None | None | None | None | N |
| R/E | 0.7536 | likely_pathogenic | 0.8547 | pathogenic | -0.023 | Destabilizing | 0.91 | D | 0.522 | neutral | None | None | None | None | N |
| R/F | 0.8453 | likely_pathogenic | 0.9069 | pathogenic | -0.56 | Destabilizing | 0.998 | D | 0.705 | prob.neutral | None | None | None | None | N |
| R/G | 0.6999 | likely_pathogenic | 0.8141 | pathogenic | -0.472 | Destabilizing | 0.939 | D | 0.617 | neutral | D | 0.536959657 | None | None | N |
| R/H | 0.2413 | likely_benign | 0.2906 | benign | -0.892 | Destabilizing | 0.998 | D | 0.611 | neutral | None | None | None | None | N |
| R/I | 0.5531 | ambiguous | 0.6884 | pathogenic | 0.181 | Stabilizing | 0.991 | D | 0.733 | prob.delet. | N | 0.514093817 | None | None | N |
| R/K | 0.1344 | likely_benign | 0.1978 | benign | -0.238 | Destabilizing | 0.046 | N | 0.208 | neutral | N | 0.480556957 | None | None | N |
| R/L | 0.6231 | likely_pathogenic | 0.7267 | pathogenic | 0.181 | Stabilizing | 0.953 | D | 0.617 | neutral | None | None | None | None | N |
| R/M | 0.5955 | likely_pathogenic | 0.7605 | pathogenic | -0.007 | Destabilizing | 0.999 | D | 0.669 | neutral | None | None | None | None | N |
| R/N | 0.8764 | likely_pathogenic | 0.9307 | pathogenic | 0.183 | Stabilizing | 0.986 | D | 0.599 | neutral | None | None | None | None | N |
| R/P | 0.9781 | likely_pathogenic | 0.9852 | pathogenic | 0.046 | Stabilizing | 0.993 | D | 0.727 | prob.delet. | None | None | None | None | N |
| R/Q | 0.2496 | likely_benign | 0.3261 | benign | -0.052 | Destabilizing | 0.986 | D | 0.605 | neutral | None | None | None | None | N |
| R/S | 0.8811 | likely_pathogenic | 0.9362 | pathogenic | -0.334 | Destabilizing | 0.939 | D | 0.654 | neutral | N | 0.481527145 | None | None | N |
| R/T | 0.6811 | likely_pathogenic | 0.8154 | pathogenic | -0.153 | Destabilizing | 0.982 | D | 0.687 | prob.neutral | N | 0.476720971 | None | None | N |
| R/V | 0.6771 | likely_pathogenic | 0.779 | pathogenic | 0.046 | Stabilizing | 0.993 | D | 0.729 | prob.delet. | None | None | None | None | N |
| R/W | 0.444 | ambiguous | 0.5344 | ambiguous | -0.507 | Destabilizing | 0.999 | D | 0.662 | neutral | None | None | None | None | N |
| R/Y | 0.7142 | likely_pathogenic | 0.7834 | pathogenic | -0.112 | Destabilizing | 0.998 | D | 0.717 | 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.