Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35640 | 107143;107144;107145 | chr2:178528833;178528832;178528831 | chr2:179393560;179393559;179393558 |
| N2AB | 33999 | 102220;102221;102222 | chr2:178528833;178528832;178528831 | chr2:179393560;179393559;179393558 |
| N2A | 33072 | 99439;99440;99441 | chr2:178528833;178528832;178528831 | chr2:179393560;179393559;179393558 |
| N2B | 26575 | 79948;79949;79950 | chr2:178528833;178528832;178528831 | chr2:179393560;179393559;179393558 |
| Novex-1 | 26700 | 80323;80324;80325 | chr2:178528833;178528832;178528831 | chr2:179393560;179393559;179393558 |
| Novex-2 | 26767 | 80524;80525;80526 | chr2:178528833;178528832;178528831 | chr2:179393560;179393559;179393558 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/P | rs750550267  |
-1.023 | 1.0 | N | 0.874 | 0.56 | 0.625352062809 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 0 | 5.66E-05 | None | 0 | 0 | None | 0 | None | 0 | 7.79E-06 | 0 |
| L/P | rs750550267 |
-1.023 | 1.0 | N | 0.874 | 0.56 | 0.625352062809 | gnomAD-4.0.0 | 2.05246E-06 | None | None | None | None | N | None | 0 | 4.47267E-05 | None | 0 | 0 | None | 0 | 0 | 8.994E-07 | 0 | 0 |
| L/R | rs750550267 |
-0.508 | 1.0 | N | 0.877 | 0.533 | 0.553226778517 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 0 | 0 |
| L/R | rs750550267 |
-0.508 | 1.0 | N | 0.877 | 0.533 | 0.553226778517 | gnomAD-4.0.0 | 2.73662E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.63736E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.7542 | likely_pathogenic | 0.7776 | pathogenic | -2.163 | Highly Destabilizing | 0.999 | D | 0.742 | deleterious | None | None | None | None | N |
| L/C | 0.7715 | likely_pathogenic | 0.8114 | pathogenic | -1.744 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| L/D | 0.9824 | likely_pathogenic | 0.9848 | pathogenic | -1.687 | Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | N |
| L/E | 0.9033 | likely_pathogenic | 0.9089 | pathogenic | -1.583 | Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| L/F | 0.3017 | likely_benign | 0.3373 | benign | -1.466 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| L/G | 0.9372 | likely_pathogenic | 0.947 | pathogenic | -2.593 | Highly Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| L/H | 0.5129 | ambiguous | 0.5452 | ambiguous | -1.874 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| L/I | 0.1619 | likely_benign | 0.1753 | benign | -0.991 | Destabilizing | 0.999 | D | 0.533 | neutral | None | None | None | None | N |
| L/K | 0.4634 | ambiguous | 0.4861 | ambiguous | -1.495 | Destabilizing | 1.0 | D | 0.864 | deleterious | None | None | None | None | N |
| L/M | 0.215 | likely_benign | 0.23 | benign | -0.987 | Destabilizing | 1.0 | D | 0.748 | deleterious | N | 0.46290516 | None | None | N |
| L/N | 0.8927 | likely_pathogenic | 0.9033 | pathogenic | -1.517 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| L/P | 0.9895 | likely_pathogenic | 0.9908 | pathogenic | -1.355 | Destabilizing | 1.0 | D | 0.874 | deleterious | N | 0.463078518 | None | None | N |
| L/Q | 0.4577 | ambiguous | 0.4746 | ambiguous | -1.567 | Destabilizing | 1.0 | D | 0.871 | deleterious | N | 0.462558443 | None | None | N |
| L/R | 0.3761 | ambiguous | 0.3917 | ambiguous | -1.069 | Destabilizing | 1.0 | D | 0.877 | deleterious | N | 0.459437993 | None | None | N |
| L/S | 0.8271 | likely_pathogenic | 0.8466 | pathogenic | -2.292 | Highly Destabilizing | 1.0 | D | 0.866 | deleterious | None | None | None | None | N |
| L/T | 0.8187 | likely_pathogenic | 0.8364 | pathogenic | -2.051 | Highly Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| L/V | 0.2195 | likely_benign | 0.2377 | benign | -1.355 | Destabilizing | 0.999 | D | 0.525 | neutral | N | 0.462211726 | None | None | N |
| L/W | 0.4221 | ambiguous | 0.4674 | ambiguous | -1.615 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| L/Y | 0.5943 | likely_pathogenic | 0.6264 | pathogenic | -1.359 | Destabilizing | 1.0 | D | 0.869 | 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.