Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23666 | 71221;71222;71223 | chr2:178575136;178575135;178575134 | chr2:179439863;179439862;179439861 |
| N2AB | 22025 | 66298;66299;66300 | chr2:178575136;178575135;178575134 | chr2:179439863;179439862;179439861 |
| N2A | 21098 | 63517;63518;63519 | chr2:178575136;178575135;178575134 | chr2:179439863;179439862;179439861 |
| N2B | 14601 | 44026;44027;44028 | chr2:178575136;178575135;178575134 | chr2:179439863;179439862;179439861 |
| Novex-1 | 14726 | 44401;44402;44403 | chr2:178575136;178575135;178575134 | chr2:179439863;179439862;179439861 |
| Novex-2 | 14793 | 44602;44603;44604 | chr2:178575136;178575135;178575134 | chr2:179439863;179439862;179439861 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs548118690  |
0.076 | 0.925 | D | 0.549 | 0.349 | 0.477529508747 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.29E-05 | None | 0 | 0 | 0 |
| T/I | rs548118690 |
0.076 | 0.925 | D | 0.549 | 0.349 | 0.477529508747 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07383E-04 | 0 |
| T/I | rs548118690 |
0.076 | 0.925 | D | 0.549 | 0.349 | 0.477529508747 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| T/I | rs548118690 |
0.076 | 0.925 | D | 0.549 | 0.349 | 0.477529508747 | gnomAD-4.0.0 | 2.56714E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.39646E-06 | 1.34452E-05 | 0 |
| T/S | None | None | 0.287 | N | 0.233 | 0.125 | 0.141422826196 | gnomAD-4.0.0 | 1.59348E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86128E-06 | 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 | 0.0881 | likely_benign | 0.0921 | benign | -0.879 | Destabilizing | 0.835 | D | 0.488 | neutral | N | 0.497822784 | None | None | N |
| T/C | 0.3148 | likely_benign | 0.3393 | benign | -0.555 | Destabilizing | 1.0 | D | 0.616 | neutral | None | None | None | None | N |
| T/D | 0.3582 | ambiguous | 0.3985 | ambiguous | -0.004 | Destabilizing | 0.97 | D | 0.585 | neutral | None | None | None | None | N |
| T/E | 0.2664 | likely_benign | 0.2889 | benign | 0.059 | Stabilizing | 0.97 | D | 0.574 | neutral | None | None | None | None | N |
| T/F | 0.1425 | likely_benign | 0.154 | benign | -0.898 | Destabilizing | 0.996 | D | 0.647 | neutral | None | None | None | None | N |
| T/G | 0.2458 | likely_benign | 0.2816 | benign | -1.174 | Destabilizing | 0.97 | D | 0.583 | neutral | None | None | None | None | N |
| T/H | 0.1943 | likely_benign | 0.2097 | benign | -1.214 | Destabilizing | 1.0 | D | 0.65 | neutral | None | None | None | None | N |
| T/I | 0.0939 | likely_benign | 0.0945 | benign | -0.171 | Destabilizing | 0.925 | D | 0.549 | neutral | D | 0.530251312 | None | None | N |
| T/K | 0.2309 | likely_benign | 0.245 | benign | -0.506 | Destabilizing | 0.961 | D | 0.579 | neutral | N | 0.497368103 | None | None | N |
| T/L | 0.0747 | likely_benign | 0.0762 | benign | -0.171 | Destabilizing | 0.871 | D | 0.546 | neutral | None | None | None | None | N |
| T/M | 0.0822 | likely_benign | 0.0836 | benign | -0.148 | Destabilizing | 0.996 | D | 0.632 | neutral | None | None | None | None | N |
| T/N | 0.1117 | likely_benign | 0.1232 | benign | -0.652 | Destabilizing | 0.97 | D | 0.583 | neutral | None | None | None | None | N |
| T/P | 0.587 | likely_pathogenic | 0.6111 | pathogenic | -0.375 | Destabilizing | 0.994 | D | 0.605 | neutral | D | 0.531526533 | None | None | N |
| T/Q | 0.2037 | likely_benign | 0.2143 | benign | -0.634 | Destabilizing | 0.996 | D | 0.622 | neutral | None | None | None | None | N |
| T/R | 0.195 | likely_benign | 0.2043 | benign | -0.385 | Destabilizing | 0.994 | D | 0.62 | neutral | D | 0.535675775 | None | None | N |
| T/S | 0.0886 | likely_benign | 0.0954 | benign | -0.996 | Destabilizing | 0.287 | N | 0.233 | neutral | N | 0.476104609 | None | None | N |
| T/V | 0.0921 | likely_benign | 0.0937 | benign | -0.375 | Destabilizing | 0.304 | N | 0.325 | neutral | None | None | None | None | N |
| T/W | 0.4733 | ambiguous | 0.5024 | ambiguous | -0.887 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| T/Y | 0.1971 | likely_benign | 0.2154 | benign | -0.609 | Destabilizing | 0.999 | D | 0.651 | 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.