Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1368 | 4327;4328;4329 | chr2:178778980;178778979;178778978 | chr2:179643707;179643706;179643705 |
| N2AB | 1368 | 4327;4328;4329 | chr2:178778980;178778979;178778978 | chr2:179643707;179643706;179643705 |
| N2A | 1368 | 4327;4328;4329 | chr2:178778980;178778979;178778978 | chr2:179643707;179643706;179643705 |
| N2B | 1322 | 4189;4190;4191 | chr2:178778980;178778979;178778978 | chr2:179643707;179643706;179643705 |
| Novex-1 | 1322 | 4189;4190;4191 | chr2:178778980;178778979;178778978 | chr2:179643707;179643706;179643705 |
| Novex-2 | 1322 | 4189;4190;4191 | chr2:178778980;178778979;178778978 | chr2:179643707;179643706;179643705 |
| Novex-3 | 1368 | 4327;4328;4329 | chr2:178778980;178778979;178778978 | chr2:179643707;179643706;179643705 |
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/H | rs1377114122  |
-0.992 | 1.0 | D | 0.732 | 0.708 | 0.356897458496 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.84E-06 | 0 |
| N/H | rs1377114122 |
-0.992 | 1.0 | D | 0.732 | 0.708 | 0.356897458496 | gnomAD-4.0.0 | 3.18159E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71389E-06 | 0 | 0 |
| N/S | rs771563848 |
-0.592 | 0.999 | N | 0.583 | 0.508 | 0.214338557667 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.62E-05 | 0 | 0 |
| N/S | rs771563848 |
-0.592 | 0.999 | N | 0.583 | 0.508 | 0.214338557667 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78469E-04 |
| N/S | rs771563848 |
-0.592 | 0.999 | N | 0.583 | 0.508 | 0.214338557667 | gnomAD-4.0.0 | 3.84216E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.56843E-05 | 0 | 0 | 0 | 5.68473E-05 |
| N/T | rs771563848 |
-0.395 | 0.999 | D | 0.699 | 0.683 | 0.463328977263 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| N/T | rs771563848 |
-0.395 | 0.999 | D | 0.699 | 0.683 | 0.463328977263 | gnomAD-4.0.0 | 1.5908E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43279E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.9936 | likely_pathogenic | 0.9891 | pathogenic | -0.487 | Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | I |
| N/C | 0.9625 | likely_pathogenic | 0.9489 | pathogenic | -0.081 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| N/D | 0.9543 | likely_pathogenic | 0.9555 | pathogenic | -1.448 | Destabilizing | 0.999 | D | 0.615 | neutral | D | 0.752397233 | None | None | I |
| N/E | 0.9986 | likely_pathogenic | 0.9981 | pathogenic | -1.413 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | I |
| N/F | 0.999 | likely_pathogenic | 0.9985 | pathogenic | -0.863 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| N/G | 0.975 | likely_pathogenic | 0.961 | pathogenic | -0.71 | Destabilizing | 0.999 | D | 0.559 | neutral | None | None | None | None | I |
| N/H | 0.959 | likely_pathogenic | 0.9438 | pathogenic | -0.784 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | D | 0.719979541 | None | None | I |
| N/I | 0.9967 | likely_pathogenic | 0.9944 | pathogenic | 0.036 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | D | 0.755514866 | None | None | I |
| N/K | 0.9993 | likely_pathogenic | 0.9988 | pathogenic | -0.045 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | D | 0.753879413 | None | None | I |
| N/L | 0.9873 | likely_pathogenic | 0.9827 | pathogenic | 0.036 | Stabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| N/M | 0.9956 | likely_pathogenic | 0.9938 | pathogenic | 0.667 | Stabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | I |
| N/P | 0.9986 | likely_pathogenic | 0.9972 | pathogenic | -0.112 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| N/Q | 0.998 | likely_pathogenic | 0.9972 | pathogenic | -1.036 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| N/R | 0.9982 | likely_pathogenic | 0.9971 | pathogenic | 0.135 | Stabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| N/S | 0.6115 | likely_pathogenic | 0.543 | ambiguous | -0.593 | Destabilizing | 0.999 | D | 0.583 | neutral | N | 0.480610136 | None | None | I |
| N/T | 0.9011 | likely_pathogenic | 0.878 | pathogenic | -0.414 | Destabilizing | 0.999 | D | 0.699 | prob.neutral | D | 0.668061344 | None | None | I |
| N/V | 0.9933 | likely_pathogenic | 0.989 | pathogenic | -0.112 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | I |
| N/W | 0.9998 | likely_pathogenic | 0.9997 | pathogenic | -0.776 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| N/Y | 0.9922 | likely_pathogenic | 0.9888 | pathogenic | -0.415 | Destabilizing | 1.0 | D | 0.745 | deleterious | D | 0.719979541 | None | None | I |
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.