Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34213 | 102862;102863;102864 | chr2:178533978;178533977;178533976 | chr2:179398705;179398704;179398703 |
| N2AB | 32572 | 97939;97940;97941 | chr2:178533978;178533977;178533976 | chr2:179398705;179398704;179398703 |
| N2A | 31645 | 95158;95159;95160 | chr2:178533978;178533977;178533976 | chr2:179398705;179398704;179398703 |
| N2B | 25148 | 75667;75668;75669 | chr2:178533978;178533977;178533976 | chr2:179398705;179398704;179398703 |
| Novex-1 | 25273 | 76042;76043;76044 | chr2:178533978;178533977;178533976 | chr2:179398705;179398704;179398703 |
| Novex-2 | 25340 | 76243;76244;76245 | chr2:178533978;178533977;178533976 | chr2:179398705;179398704;179398703 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/S | rs375332499  |
-0.752 | 0.449 | N | 0.259 | 0.253 | None | gnomAD-2.1.1 | 8.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.77E-05 | 0 |
| N/S | rs375332499 |
-0.752 | 0.449 | N | 0.259 | 0.253 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| N/S | rs375332499 |
-0.752 | 0.449 | N | 0.259 | 0.253 | None | gnomAD-4.0.0 | 3.0982E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69512E-06 | 1.09782E-05 | 3.20205E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.9869 | likely_pathogenic | 0.9743 | pathogenic | -0.626 | Destabilizing | 0.931 | D | 0.577 | neutral | None | None | None | None | N |
| N/C | 0.9618 | likely_pathogenic | 0.9415 | pathogenic | -0.314 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| N/D | 0.7831 | likely_pathogenic | 0.7195 | pathogenic | -1.832 | Destabilizing | 0.98 | D | 0.575 | neutral | N | 0.485766964 | None | None | N |
| N/E | 0.9958 | likely_pathogenic | 0.992 | pathogenic | -1.705 | Destabilizing | 0.985 | D | 0.575 | neutral | None | None | None | None | N |
| N/F | 0.9988 | likely_pathogenic | 0.9979 | pathogenic | -0.648 | Destabilizing | 0.999 | D | 0.722 | prob.delet. | None | None | None | None | N |
| N/G | 0.9369 | likely_pathogenic | 0.8866 | pathogenic | -0.939 | Destabilizing | 0.964 | D | 0.569 | neutral | None | None | None | None | N |
| N/H | 0.9371 | likely_pathogenic | 0.8799 | pathogenic | -0.793 | Destabilizing | 0.999 | D | 0.601 | neutral | N | 0.509911607 | None | None | N |
| N/I | 0.9945 | likely_pathogenic | 0.9912 | pathogenic | 0.16 | Stabilizing | 0.997 | D | 0.723 | prob.delet. | N | 0.498808791 | None | None | N |
| N/K | 0.9961 | likely_pathogenic | 0.9911 | pathogenic | -0.158 | Destabilizing | 0.98 | D | 0.577 | neutral | N | 0.509404628 | None | None | N |
| N/L | 0.9769 | likely_pathogenic | 0.9631 | pathogenic | 0.16 | Stabilizing | 0.993 | D | 0.709 | prob.delet. | None | None | None | None | N |
| N/M | 0.9893 | likely_pathogenic | 0.9839 | pathogenic | 0.564 | Stabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | N |
| N/P | 0.9977 | likely_pathogenic | 0.9959 | pathogenic | -0.074 | Destabilizing | 0.998 | D | 0.691 | prob.neutral | None | None | None | None | N |
| N/Q | 0.995 | likely_pathogenic | 0.9897 | pathogenic | -1.095 | Destabilizing | 0.998 | D | 0.639 | neutral | None | None | None | None | N |
| N/R | 0.9947 | likely_pathogenic | 0.9889 | pathogenic | -0.123 | Destabilizing | 0.998 | D | 0.652 | neutral | None | None | None | None | N |
| N/S | 0.4399 | ambiguous | 0.3512 | ambiguous | -0.922 | Destabilizing | 0.449 | N | 0.259 | neutral | N | 0.513614487 | None | None | N |
| N/T | 0.8129 | likely_pathogenic | 0.742 | pathogenic | -0.631 | Destabilizing | 0.961 | D | 0.557 | neutral | N | 0.508897649 | None | None | N |
| N/V | 0.9933 | likely_pathogenic | 0.9894 | pathogenic | -0.074 | Destabilizing | 0.998 | D | 0.715 | prob.delet. | None | None | None | None | N |
| N/W | 0.9994 | likely_pathogenic | 0.999 | pathogenic | -0.576 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| N/Y | 0.9861 | likely_pathogenic | 0.9752 | pathogenic | -0.183 | Destabilizing | 0.999 | D | 0.683 | prob.neutral | N | 0.498555301 | 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.