Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14412 | 43459;43460;43461 | chr2:178632772;178632771;178632770 | chr2:179497499;179497498;179497497 |
| N2AB | 12771 | 38536;38537;38538 | chr2:178632772;178632771;178632770 | chr2:179497499;179497498;179497497 |
| N2A | 11844 | 35755;35756;35757 | chr2:178632772;178632771;178632770 | chr2:179497499;179497498;179497497 |
| N2B | 5347 | 16264;16265;16266 | chr2:178632772;178632771;178632770 | chr2:179497499;179497498;179497497 |
| Novex-1 | 5472 | 16639;16640;16641 | chr2:178632772;178632771;178632770 | chr2:179497499;179497498;179497497 |
| Novex-2 | 5539 | 16840;16841;16842 | chr2:178632772;178632771;178632770 | chr2:179497499;179497498;179497497 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs185007509  |
-0.705 | 0.999 | N | 0.545 | 0.367 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93723E-04 | None | 0 | 0 | 0 | 0 | 0 |
| T/A | rs185007509 |
-0.705 | 0.999 | N | 0.545 | 0.367 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| T/A | rs185007509 |
-0.705 | 0.999 | N | 0.545 | 0.367 | None | gnomAD-4.0.0 | 2.56442E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.85885E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1213 | likely_benign | 0.1173 | benign | -0.793 | Destabilizing | 0.999 | D | 0.545 | neutral | N | 0.510762249 | None | None | N |
| T/C | 0.6261 | likely_pathogenic | 0.5727 | pathogenic | -0.468 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | N |
| T/D | 0.5589 | ambiguous | 0.5619 | ambiguous | -0.177 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | N |
| T/E | 0.377 | ambiguous | 0.3884 | ambiguous | -0.152 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| T/F | 0.3276 | likely_benign | 0.2946 | benign | -0.688 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| T/G | 0.5117 | ambiguous | 0.4787 | ambiguous | -1.084 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| T/H | 0.271 | likely_benign | 0.25 | benign | -1.262 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| T/I | 0.1849 | likely_benign | 0.1958 | benign | -0.1 | Destabilizing | 1.0 | D | 0.779 | deleterious | N | 0.510762249 | None | None | N |
| T/K | 0.1672 | likely_benign | 0.1865 | benign | -0.743 | Destabilizing | 1.0 | D | 0.784 | deleterious | N | 0.442033576 | None | None | N |
| T/L | 0.1303 | likely_benign | 0.1194 | benign | -0.1 | Destabilizing | 0.999 | D | 0.665 | neutral | None | None | None | None | N |
| T/M | 0.1116 | likely_benign | 0.105 | benign | 0.072 | Stabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| T/N | 0.1588 | likely_benign | 0.1561 | benign | -0.727 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| T/P | 0.4485 | ambiguous | 0.4824 | ambiguous | -0.298 | Destabilizing | 1.0 | D | 0.775 | deleterious | D | 0.58543109 | None | None | N |
| T/Q | 0.2454 | likely_benign | 0.2399 | benign | -0.823 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| T/R | 0.1419 | likely_benign | 0.1445 | benign | -0.532 | Destabilizing | 1.0 | D | 0.776 | deleterious | N | 0.460096962 | None | None | N |
| T/S | 0.1629 | likely_benign | 0.1485 | benign | -1.023 | Destabilizing | 0.999 | D | 0.53 | neutral | N | 0.505396097 | None | None | N |
| T/V | 0.1706 | likely_benign | 0.1765 | benign | -0.298 | Destabilizing | 0.999 | D | 0.575 | neutral | None | None | None | None | N |
| T/W | 0.7574 | likely_pathogenic | 0.7099 | pathogenic | -0.646 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| T/Y | 0.3584 | ambiguous | 0.3362 | benign | -0.419 | Destabilizing | 1.0 | D | 0.778 | 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.