Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1123 | 3592;3593;3594 | chr2:178782225;178782224;178782223 | chr2:179646952;179646951;179646950 |
| N2AB | 1123 | 3592;3593;3594 | chr2:178782225;178782224;178782223 | chr2:179646952;179646951;179646950 |
| N2A | 1123 | 3592;3593;3594 | chr2:178782225;178782224;178782223 | chr2:179646952;179646951;179646950 |
| N2B | 1077 | 3454;3455;3456 | chr2:178782225;178782224;178782223 | chr2:179646952;179646951;179646950 |
| Novex-1 | 1077 | 3454;3455;3456 | chr2:178782225;178782224;178782223 | chr2:179646952;179646951;179646950 |
| Novex-2 | 1077 | 3454;3455;3456 | chr2:178782225;178782224;178782223 | chr2:179646952;179646951;179646950 |
| Novex-3 | 1123 | 3592;3593;3594 | chr2:178782225;178782224;178782223 | chr2:179646952;179646951;179646950 |
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 | None | None | 0.898 | N | 0.481 | 0.212 | 0.281381271821 | gnomAD-4.0.0 | 1.59055E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43271E-05 | 0 |
| T/N | None | None | 0.993 | N | 0.569 | 0.273 | 0.47737504017 | gnomAD-4.0.0 | 6.8408E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99308E-07 | 0 | 0 |
| T/S | rs773799748  |
-0.067 | 0.362 | N | 0.299 | 0.187 | 0.218845423259 | gnomAD-2.1.1 | 2.79E-05 | None | None | None | None | N | None | 0 | 0 | None | 6.95825E-04 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/S | rs773799748 |
-0.067 | 0.362 | N | 0.299 | 0.187 | 0.218845423259 | gnomAD-3.1.2 | 7.23E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 2.88184E-03 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/S | rs773799748 |
-0.067 | 0.362 | N | 0.299 | 0.187 | 0.218845423259 | gnomAD-4.0.0 | 3.18111E-06 | None | None | None | None | N | None | 0 | 4.57247E-05 | None | 0 | 0 | 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 | 0.3376 | likely_benign | 0.2512 | benign | -0.182 | Destabilizing | 0.898 | D | 0.481 | neutral | N | 0.471121447 | None | None | N |
| T/C | 0.9321 | likely_pathogenic | 0.896 | pathogenic | -0.358 | Destabilizing | 1.0 | D | 0.599 | neutral | None | None | None | None | N |
| T/D | 0.9101 | likely_pathogenic | 0.8713 | pathogenic | 0.304 | Stabilizing | 0.995 | D | 0.595 | neutral | None | None | None | None | N |
| T/E | 0.8668 | likely_pathogenic | 0.8032 | pathogenic | 0.229 | Stabilizing | 0.995 | D | 0.587 | neutral | None | None | None | None | N |
| T/F | 0.8235 | likely_pathogenic | 0.7628 | pathogenic | -0.831 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | N |
| T/G | 0.6474 | likely_pathogenic | 0.5621 | ambiguous | -0.263 | Destabilizing | 0.966 | D | 0.559 | neutral | None | None | None | None | N |
| T/H | 0.7781 | likely_pathogenic | 0.699 | pathogenic | -0.452 | Destabilizing | 1.0 | D | 0.617 | neutral | None | None | None | None | N |
| T/I | 0.7312 | likely_pathogenic | 0.6603 | pathogenic | -0.091 | Destabilizing | 0.997 | D | 0.639 | neutral | N | 0.496117722 | None | None | N |
| T/K | 0.755 | likely_pathogenic | 0.6632 | pathogenic | -0.181 | Destabilizing | 0.995 | D | 0.595 | neutral | None | None | None | None | N |
| T/L | 0.4145 | ambiguous | 0.3449 | ambiguous | -0.091 | Destabilizing | 0.983 | D | 0.582 | neutral | None | None | None | None | N |
| T/M | 0.3234 | likely_benign | 0.2622 | benign | -0.178 | Destabilizing | 1.0 | D | 0.617 | neutral | None | None | None | None | N |
| T/N | 0.5078 | ambiguous | 0.4224 | ambiguous | -0.065 | Destabilizing | 0.993 | D | 0.569 | neutral | N | 0.470069013 | None | None | N |
| T/P | 0.4546 | ambiguous | 0.3629 | ambiguous | -0.096 | Destabilizing | 0.997 | D | 0.632 | neutral | N | 0.442173401 | None | None | N |
| T/Q | 0.6833 | likely_pathogenic | 0.5955 | pathogenic | -0.208 | Destabilizing | 0.998 | D | 0.631 | neutral | None | None | None | None | N |
| T/R | 0.7223 | likely_pathogenic | 0.6167 | pathogenic | 0.036 | Stabilizing | 0.995 | D | 0.615 | neutral | None | None | None | None | N |
| T/S | 0.3491 | ambiguous | 0.286 | benign | -0.245 | Destabilizing | 0.362 | N | 0.299 | neutral | N | 0.424868993 | None | None | N |
| T/V | 0.5329 | ambiguous | 0.4682 | ambiguous | -0.096 | Destabilizing | 0.983 | D | 0.525 | neutral | None | None | None | None | N |
| T/W | 0.9625 | likely_pathogenic | 0.9437 | pathogenic | -0.923 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | N |
| T/Y | 0.8596 | likely_pathogenic | 0.8087 | pathogenic | -0.582 | Destabilizing | 0.999 | D | 0.647 | neutral | 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.