Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32913 | 98962;98963;98964 | chr2:178539198;178539197;178539196 | chr2:179403925;179403924;179403923 |
| N2AB | 31272 | 94039;94040;94041 | chr2:178539198;178539197;178539196 | chr2:179403925;179403924;179403923 |
| N2A | 30345 | 91258;91259;91260 | chr2:178539198;178539197;178539196 | chr2:179403925;179403924;179403923 |
| N2B | 23848 | 71767;71768;71769 | chr2:178539198;178539197;178539196 | chr2:179403925;179403924;179403923 |
| Novex-1 | 23973 | 72142;72143;72144 | chr2:178539198;178539197;178539196 | chr2:179403925;179403924;179403923 |
| Novex-2 | 24040 | 72343;72344;72345 | chr2:178539198;178539197;178539196 | chr2:179403925;179403924;179403923 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/F | None | None | 0.988 | N | 0.608 | 0.484 | 0.775252716994 | gnomAD-4.0.0 | 1.36845E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79898E-06 | 0 | 0 |
| S/Y | rs749035234  |
-0.847 | 0.996 | N | 0.609 | 0.463 | 0.758241242785 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/Y | rs749035234 |
-0.847 | 0.996 | N | 0.609 | 0.463 | 0.758241242785 | gnomAD-4.0.0 | 6.84224E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.51965E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.132 | likely_benign | 0.1593 | benign | -0.634 | Destabilizing | 0.675 | D | 0.329 | neutral | N | 0.483710411 | None | None | N |
| S/C | 0.19 | likely_benign | 0.2114 | benign | -0.823 | Destabilizing | 0.999 | D | 0.525 | neutral | N | 0.48903001 | None | None | N |
| S/D | 0.8991 | likely_pathogenic | 0.9155 | pathogenic | -1.271 | Destabilizing | 0.969 | D | 0.463 | neutral | None | None | None | None | N |
| S/E | 0.8932 | likely_pathogenic | 0.9222 | pathogenic | -1.267 | Destabilizing | 0.969 | D | 0.425 | neutral | None | None | None | None | N |
| S/F | 0.5168 | ambiguous | 0.563 | ambiguous | -1.138 | Destabilizing | 0.988 | D | 0.608 | neutral | N | 0.502930756 | None | None | N |
| S/G | 0.2333 | likely_benign | 0.259 | benign | -0.825 | Destabilizing | 0.969 | D | 0.385 | neutral | None | None | None | None | N |
| S/H | 0.6739 | likely_pathogenic | 0.7126 | pathogenic | -1.393 | Destabilizing | 0.999 | D | 0.524 | neutral | None | None | None | None | N |
| S/I | 0.5986 | likely_pathogenic | 0.6544 | pathogenic | -0.23 | Destabilizing | 0.884 | D | 0.519 | neutral | None | None | None | None | N |
| S/K | 0.9458 | likely_pathogenic | 0.963 | pathogenic | -0.63 | Destabilizing | 0.939 | D | 0.427 | neutral | None | None | None | None | N |
| S/L | 0.2841 | likely_benign | 0.3084 | benign | -0.23 | Destabilizing | 0.759 | D | 0.457 | neutral | None | None | None | None | N |
| S/M | 0.3717 | ambiguous | 0.3724 | ambiguous | 0.098 | Stabilizing | 0.991 | D | 0.545 | neutral | None | None | None | None | N |
| S/N | 0.4556 | ambiguous | 0.4839 | ambiguous | -0.848 | Destabilizing | 0.969 | D | 0.477 | neutral | None | None | None | None | N |
| S/P | 0.9957 | likely_pathogenic | 0.9966 | pathogenic | -0.335 | Destabilizing | 0.996 | D | 0.557 | neutral | D | 0.542430949 | None | None | N |
| S/Q | 0.8005 | likely_pathogenic | 0.8334 | pathogenic | -1.135 | Destabilizing | 0.997 | D | 0.501 | neutral | None | None | None | None | N |
| S/R | 0.9112 | likely_pathogenic | 0.9408 | pathogenic | -0.449 | Destabilizing | 0.991 | D | 0.567 | neutral | None | None | None | None | N |
| S/T | 0.1007 | likely_benign | 0.0989 | benign | -0.733 | Destabilizing | 0.061 | N | 0.1 | neutral | N | 0.494820869 | None | None | N |
| S/V | 0.4714 | ambiguous | 0.508 | ambiguous | -0.335 | Destabilizing | 0.17 | N | 0.385 | neutral | None | None | None | None | N |
| S/W | 0.7631 | likely_pathogenic | 0.7941 | pathogenic | -1.172 | Destabilizing | 0.999 | D | 0.654 | neutral | None | None | None | None | N |
| S/Y | 0.5208 | ambiguous | 0.5686 | pathogenic | -0.811 | Destabilizing | 0.996 | D | 0.609 | neutral | N | 0.487762563 | 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.