Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32442 | 97549;97550;97551 | chr2:178542432;178542431;178542430 | chr2:179407159;179407158;179407157 |
| N2AB | 30801 | 92626;92627;92628 | chr2:178542432;178542431;178542430 | chr2:179407159;179407158;179407157 |
| N2A | 29874 | 89845;89846;89847 | chr2:178542432;178542431;178542430 | chr2:179407159;179407158;179407157 |
| N2B | 23377 | 70354;70355;70356 | chr2:178542432;178542431;178542430 | chr2:179407159;179407158;179407157 |
| Novex-1 | 23502 | 70729;70730;70731 | chr2:178542432;178542431;178542430 | chr2:179407159;179407158;179407157 |
| Novex-2 | 23569 | 70930;70931;70932 | chr2:178542432;178542431;178542430 | chr2:179407159;179407158;179407157 |
| 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/S | rs778341120  |
None | 1.0 | N | 0.614 | 0.302 | 0.376393476264 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/S | rs778341120 |
None | 1.0 | N | 0.614 | 0.302 | 0.376393476264 | gnomAD-4.0.0 | 1.85924E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54297E-06 | 0 | 0 |
| A/T | rs778341120 |
-0.984 | 1.0 | N | 0.672 | 0.417 | None | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.23E-05 | 0 |
| A/T | rs778341120 |
-0.984 | 1.0 | N | 0.672 | 0.417 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| A/T | rs778341120 |
-0.984 | 1.0 | N | 0.672 | 0.417 | None | gnomAD-4.0.0 | 1.73529E-05 | None | None | None | None | N | None | 5.34045E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.78008E-05 | 0 | 4.80384E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6535 | likely_pathogenic | 0.5958 | pathogenic | -0.709 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| A/D | 0.9071 | likely_pathogenic | 0.8593 | pathogenic | -1.636 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | N | 0.511072827 | None | None | N |
| A/E | 0.8309 | likely_pathogenic | 0.7671 | pathogenic | -1.681 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | N |
| A/F | 0.777 | likely_pathogenic | 0.7037 | pathogenic | -1.156 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| A/G | 0.3474 | ambiguous | 0.2932 | benign | -1.309 | Destabilizing | 1.0 | D | 0.604 | neutral | N | 0.503224135 | None | None | N |
| A/H | 0.894 | likely_pathogenic | 0.8597 | pathogenic | -1.524 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | N |
| A/I | 0.4856 | ambiguous | 0.3977 | ambiguous | -0.569 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| A/K | 0.9106 | likely_pathogenic | 0.8732 | pathogenic | -1.439 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | N |
| A/L | 0.5229 | ambiguous | 0.4269 | ambiguous | -0.569 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| A/M | 0.5505 | ambiguous | 0.4477 | ambiguous | -0.279 | Destabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | N |
| A/N | 0.7489 | likely_pathogenic | 0.6804 | pathogenic | -1.051 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| A/P | 0.7384 | likely_pathogenic | 0.6651 | pathogenic | -0.699 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | N | 0.481771427 | None | None | N |
| A/Q | 0.8143 | likely_pathogenic | 0.7588 | pathogenic | -1.258 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| A/R | 0.8476 | likely_pathogenic | 0.8009 | pathogenic | -0.977 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| A/S | 0.1651 | likely_benign | 0.1498 | benign | -1.306 | Destabilizing | 1.0 | D | 0.614 | neutral | N | 0.453526033 | None | None | N |
| A/T | 0.2241 | likely_benign | 0.1753 | benign | -1.284 | Destabilizing | 1.0 | D | 0.672 | neutral | N | 0.402001135 | None | None | N |
| A/V | 0.2736 | likely_benign | 0.2139 | benign | -0.699 | Destabilizing | 1.0 | D | 0.651 | neutral | N | 0.44340504 | None | None | N |
| A/W | 0.9621 | likely_pathogenic | 0.9438 | pathogenic | -1.519 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| A/Y | 0.8753 | likely_pathogenic | 0.8289 | pathogenic | -1.172 | Destabilizing | 1.0 | D | 0.709 | 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.