Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14619 | 44080;44081;44082 | chr2:178631193;178631192;178631191 | chr2:179495920;179495919;179495918 |
| N2AB | 12978 | 39157;39158;39159 | chr2:178631193;178631192;178631191 | chr2:179495920;179495919;179495918 |
| N2A | 12051 | 36376;36377;36378 | chr2:178631193;178631192;178631191 | chr2:179495920;179495919;179495918 |
| N2B | 5554 | 16885;16886;16887 | chr2:178631193;178631192;178631191 | chr2:179495920;179495919;179495918 |
| Novex-1 | 5679 | 17260;17261;17262 | chr2:178631193;178631192;178631191 | chr2:179495920;179495919;179495918 |
| Novex-2 | 5746 | 17461;17462;17463 | chr2:178631193;178631192;178631191 | chr2:179495920;179495919;179495918 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/I | None | None | 0.811 | N | 0.549 | 0.258 | 0.477838726898 | gnomAD-4.0.0 | 1.36891E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79922E-06 | 0 | 0 |
| F/L | rs202179380  |
None | 0.379 | N | 0.543 | 0.15 | 0.374076547971 | 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 |
| F/L | rs202179380 |
None | 0.379 | N | 0.543 | 0.15 | 0.374076547971 | gnomAD-4.0.0 | 6.84455E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99609E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.7876 | likely_pathogenic | 0.7938 | pathogenic | -2.622 | Highly Destabilizing | 0.919 | D | 0.651 | neutral | None | None | None | None | N |
| F/C | 0.4679 | ambiguous | 0.4771 | ambiguous | -1.509 | Destabilizing | 0.999 | D | 0.733 | prob.delet. | D | 0.666461028 | None | None | N |
| F/D | 0.8922 | likely_pathogenic | 0.9103 | pathogenic | -1.857 | Destabilizing | 0.996 | D | 0.772 | deleterious | None | None | None | None | N |
| F/E | 0.8088 | likely_pathogenic | 0.8372 | pathogenic | -1.754 | Destabilizing | 0.988 | D | 0.759 | deleterious | None | None | None | None | N |
| F/G | 0.8927 | likely_pathogenic | 0.8985 | pathogenic | -2.972 | Highly Destabilizing | 0.988 | D | 0.729 | prob.delet. | None | None | None | None | N |
| F/H | 0.608 | likely_pathogenic | 0.6184 | pathogenic | -1.227 | Destabilizing | 0.988 | D | 0.693 | prob.neutral | None | None | None | None | N |
| F/I | 0.2881 | likely_benign | 0.3084 | benign | -1.54 | Destabilizing | 0.811 | D | 0.549 | neutral | N | 0.506627612 | None | None | N |
| F/K | 0.7836 | likely_pathogenic | 0.7985 | pathogenic | -1.423 | Destabilizing | 0.976 | D | 0.757 | deleterious | None | None | None | None | N |
| F/L | 0.7572 | likely_pathogenic | 0.7525 | pathogenic | -1.54 | Destabilizing | 0.379 | N | 0.543 | neutral | N | 0.447708667 | None | None | N |
| F/M | 0.4063 | ambiguous | 0.4402 | ambiguous | -1.272 | Destabilizing | 0.702 | D | 0.422 | neutral | None | None | None | None | N |
| F/N | 0.6984 | likely_pathogenic | 0.7217 | pathogenic | -1.485 | Destabilizing | 0.996 | D | 0.769 | deleterious | None | None | None | None | N |
| F/P | 0.9988 | likely_pathogenic | 0.9988 | pathogenic | -1.899 | Destabilizing | 0.996 | D | 0.773 | deleterious | None | None | None | None | N |
| F/Q | 0.7132 | likely_pathogenic | 0.7436 | pathogenic | -1.637 | Destabilizing | 0.988 | D | 0.771 | deleterious | None | None | None | None | N |
| F/R | 0.691 | likely_pathogenic | 0.7185 | pathogenic | -0.695 | Destabilizing | 0.988 | D | 0.769 | deleterious | None | None | None | None | N |
| F/S | 0.6147 | likely_pathogenic | 0.6255 | pathogenic | -2.286 | Highly Destabilizing | 0.984 | D | 0.704 | prob.neutral | N | 0.438648386 | None | None | N |
| F/T | 0.6808 | likely_pathogenic | 0.7122 | pathogenic | -2.091 | Highly Destabilizing | 0.976 | D | 0.707 | prob.neutral | None | None | None | None | N |
| F/V | 0.334 | likely_benign | 0.3522 | ambiguous | -1.899 | Destabilizing | 0.811 | D | 0.62 | neutral | N | 0.519785021 | None | None | N |
| F/W | 0.4973 | ambiguous | 0.4818 | ambiguous | -0.54 | Destabilizing | 0.999 | D | 0.581 | neutral | None | None | None | None | N |
| F/Y | 0.1569 | likely_benign | 0.1569 | benign | -0.772 | Destabilizing | 0.103 | N | 0.359 | neutral | N | 0.435312202 | 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.