Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28121 | 84586;84587;84588 | chr2:178561771;178561770;178561769 | chr2:179426498;179426497;179426496 |
| N2AB | 26480 | 79663;79664;79665 | chr2:178561771;178561770;178561769 | chr2:179426498;179426497;179426496 |
| N2A | 25553 | 76882;76883;76884 | chr2:178561771;178561770;178561769 | chr2:179426498;179426497;179426496 |
| N2B | 19056 | 57391;57392;57393 | chr2:178561771;178561770;178561769 | chr2:179426498;179426497;179426496 |
| Novex-1 | 19181 | 57766;57767;57768 | chr2:178561771;178561770;178561769 | chr2:179426498;179426497;179426496 |
| Novex-2 | 19248 | 57967;57968;57969 | chr2:178561771;178561770;178561769 | chr2:179426498;179426497;179426496 |
| 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 | None | None | 0.939 | N | 0.431 | 0.3 | 0.32980341726 | gnomAD-4.0.0 | 6.843E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99518E-07 | 0 | 0 |
| T/K | rs397517726  |
-0.3 | 0.521 | N | 0.338 | 0.229 | 0.269111216191 | gnomAD-2.1.1 | 2.15E-05 | None | None | None | None | N | None | 0 | 1.41611E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.40845E-04 |
| T/K | rs397517726 |
-0.3 | 0.521 | N | 0.338 | 0.229 | 0.269111216191 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 2.41E-05 | 2.61986E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 9.56938E-04 |
| T/K | rs397517726 |
-0.3 | 0.521 | N | 0.338 | 0.229 | 0.269111216191 | gnomAD-4.0.0 | 1.05359E-05 | None | None | None | None | N | None | 1.33483E-05 | 1.83394E-04 | None | 0 | 0 | None | 0 | 0 | 8.4764E-07 | 0 | 6.40451E-05 |
| T/R | rs397517726 |
0.045 | 0.684 | N | 0.433 | 0.291 | 0.33110744837 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/R | rs397517726 |
0.045 | 0.684 | N | 0.433 | 0.291 | 0.33110744837 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/R | rs397517726 |
0.045 | 0.684 | N | 0.433 | 0.291 | 0.33110744837 | gnomAD-4.0.0 | 1.23942E-06 | None | None | None | None | N | None | 2.66532E-05 | 0 | 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 | 0.0704 | likely_benign | 0.0703 | benign | -0.518 | Destabilizing | 0.472 | N | 0.413 | neutral | N | 0.443634326 | None | None | N |
| T/C | 0.4384 | ambiguous | 0.4429 | ambiguous | -0.164 | Destabilizing | 0.996 | D | 0.412 | neutral | None | None | None | None | N |
| T/D | 0.5203 | ambiguous | 0.5065 | ambiguous | -0.318 | Destabilizing | 0.59 | D | 0.33 | neutral | None | None | None | None | N |
| T/E | 0.2972 | likely_benign | 0.2804 | benign | -0.41 | Destabilizing | 0.009 | N | 0.244 | neutral | None | None | None | None | N |
| T/F | 0.3797 | ambiguous | 0.3985 | ambiguous | -1.127 | Destabilizing | 0.984 | D | 0.47 | neutral | None | None | None | None | N |
| T/G | 0.2552 | likely_benign | 0.2566 | benign | -0.621 | Destabilizing | 0.742 | D | 0.424 | neutral | None | None | None | None | N |
| T/H | 0.2783 | likely_benign | 0.2666 | benign | -1.061 | Destabilizing | 0.953 | D | 0.464 | neutral | None | None | None | None | N |
| T/I | 0.2342 | likely_benign | 0.2419 | benign | -0.362 | Destabilizing | 0.939 | D | 0.431 | neutral | N | 0.474152021 | None | None | N |
| T/K | 0.1421 | likely_benign | 0.1268 | benign | -0.395 | Destabilizing | 0.521 | D | 0.338 | neutral | N | 0.465839183 | None | None | N |
| T/L | 0.1306 | likely_benign | 0.135 | benign | -0.362 | Destabilizing | 0.742 | D | 0.393 | neutral | None | None | None | None | N |
| T/M | 0.1042 | likely_benign | 0.1013 | benign | 0.155 | Stabilizing | 0.984 | D | 0.412 | neutral | None | None | None | None | N |
| T/N | 0.1628 | likely_benign | 0.1549 | benign | -0.176 | Destabilizing | 0.742 | D | 0.438 | neutral | None | None | None | None | N |
| T/P | 0.0957 | likely_benign | 0.0906 | benign | -0.388 | Destabilizing | 0.939 | D | 0.42 | neutral | N | 0.388287184 | None | None | N |
| T/Q | 0.1836 | likely_benign | 0.1735 | benign | -0.534 | Destabilizing | 0.101 | N | 0.25 | neutral | None | None | None | None | N |
| T/R | 0.1201 | likely_benign | 0.1091 | benign | -0.059 | Destabilizing | 0.684 | D | 0.433 | neutral | N | 0.46787941 | None | None | N |
| T/S | 0.1208 | likely_benign | 0.1247 | benign | -0.33 | Destabilizing | 0.472 | N | 0.437 | neutral | N | 0.487561249 | None | None | N |
| T/V | 0.1533 | likely_benign | 0.1586 | benign | -0.388 | Destabilizing | 0.854 | D | 0.389 | neutral | None | None | None | None | N |
| T/W | 0.6943 | likely_pathogenic | 0.7025 | pathogenic | -1.097 | Destabilizing | 0.996 | D | 0.506 | neutral | None | None | None | None | N |
| T/Y | 0.3756 | ambiguous | 0.3729 | ambiguous | -0.82 | Destabilizing | 0.984 | D | 0.464 | 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.