Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27580 | 82963;82964;82965 | chr2:178563394;178563393;178563392 | chr2:179428121;179428120;179428119 |
| N2AB | 25939 | 78040;78041;78042 | chr2:178563394;178563393;178563392 | chr2:179428121;179428120;179428119 |
| N2A | 25012 | 75259;75260;75261 | chr2:178563394;178563393;178563392 | chr2:179428121;179428120;179428119 |
| N2B | 18515 | 55768;55769;55770 | chr2:178563394;178563393;178563392 | chr2:179428121;179428120;179428119 |
| Novex-1 | 18640 | 56143;56144;56145 | chr2:178563394;178563393;178563392 | chr2:179428121;179428120;179428119 |
| Novex-2 | 18707 | 56344;56345;56346 | chr2:178563394;178563393;178563392 | chr2:179428121;179428120;179428119 |
| 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/M | rs748535477  |
0.019 | 0.981 | N | 0.631 | 0.317 | 0.570930671769 | gnomAD-2.1.1 | 6.08E-05 | None | None | None | None | N | None | 0 | 5.66E-05 | None | 0 | 1.5456E-04 | None | 2.61438E-04 | None | 0 | 3.14E-05 | 0 |
| T/M | rs748535477 |
0.019 | 0.981 | N | 0.631 | 0.317 | 0.570930671769 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93723E-04 | None | 0 | 0 | 0 | 2.07383E-04 | 0 |
| T/M | rs748535477 |
0.019 | 0.981 | N | 0.631 | 0.317 | 0.570930671769 | gnomAD-4.0.0 | 2.72716E-05 | None | None | None | None | N | None | 1.33593E-05 | 3.33622E-05 | None | 0 | 4.46628E-05 | None | 0 | 0 | 1.44104E-05 | 2.08612E-04 | 4.80415E-05 |
| T/S | None | None | 0.565 | N | 0.505 | 0.105 | 0.141422826196 | gnomAD-4.0.0 | 3.18309E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85855E-06 | 1.43275E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1098 | likely_benign | 0.1005 | benign | -0.594 | Destabilizing | 0.008 | N | 0.161 | neutral | N | 0.504533644 | None | None | N |
| T/C | 0.4101 | ambiguous | 0.4021 | ambiguous | -0.356 | Destabilizing | 0.989 | D | 0.618 | neutral | None | None | None | None | N |
| T/D | 0.6342 | likely_pathogenic | 0.5687 | pathogenic | 0.037 | Stabilizing | 0.923 | D | 0.586 | neutral | None | None | None | None | N |
| T/E | 0.4451 | ambiguous | 0.3869 | ambiguous | -0.027 | Destabilizing | 0.633 | D | 0.548 | neutral | None | None | None | None | N |
| T/F | 0.2722 | likely_benign | 0.2583 | benign | -0.977 | Destabilizing | 0.923 | D | 0.699 | prob.neutral | None | None | None | None | N |
| T/G | 0.3371 | likely_benign | 0.3143 | benign | -0.754 | Destabilizing | 0.633 | D | 0.602 | neutral | None | None | None | None | N |
| T/H | 0.4003 | ambiguous | 0.3605 | ambiguous | -1.043 | Destabilizing | 0.989 | D | 0.678 | prob.neutral | None | None | None | None | N |
| T/I | 0.1107 | likely_benign | 0.1122 | benign | -0.284 | Destabilizing | 0.633 | D | 0.558 | neutral | None | None | None | None | N |
| T/K | 0.3002 | likely_benign | 0.2592 | benign | -0.501 | Destabilizing | 0.046 | N | 0.251 | neutral | N | 0.517230795 | None | None | N |
| T/L | 0.0789 | likely_benign | 0.0856 | benign | -0.284 | Destabilizing | 0.011 | N | 0.258 | neutral | None | None | None | None | N |
| T/M | 0.0758 | likely_benign | 0.0788 | benign | 0.027 | Stabilizing | 0.981 | D | 0.631 | neutral | N | 0.470967619 | None | None | N |
| T/N | 0.2091 | likely_benign | 0.1928 | benign | -0.308 | Destabilizing | 0.923 | D | 0.527 | neutral | None | None | None | None | N |
| T/P | 0.5493 | ambiguous | 0.4476 | ambiguous | -0.358 | Destabilizing | 0.949 | D | 0.635 | neutral | N | 0.500681669 | None | None | N |
| T/Q | 0.3125 | likely_benign | 0.2812 | benign | -0.579 | Destabilizing | 0.923 | D | 0.648 | neutral | None | None | None | None | N |
| T/R | 0.2538 | likely_benign | 0.2188 | benign | -0.178 | Destabilizing | 0.921 | D | 0.583 | neutral | N | 0.478334225 | None | None | N |
| T/S | 0.1513 | likely_benign | 0.142 | benign | -0.564 | Destabilizing | 0.565 | D | 0.505 | neutral | N | 0.456795625 | None | None | N |
| T/V | 0.0942 | likely_benign | 0.0982 | benign | -0.358 | Destabilizing | 0.633 | D | 0.467 | neutral | None | None | None | None | N |
| T/W | 0.6429 | likely_pathogenic | 0.6122 | pathogenic | -0.909 | Destabilizing | 0.996 | D | 0.759 | deleterious | None | None | None | None | N |
| T/Y | 0.3969 | ambiguous | 0.3608 | ambiguous | -0.662 | Destabilizing | 0.987 | D | 0.701 | prob.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.