Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25983 | 78172;78173;78174 | chr2:178568185;178568184;178568183 | chr2:179432912;179432911;179432910 |
| N2AB | 24342 | 73249;73250;73251 | chr2:178568185;178568184;178568183 | chr2:179432912;179432911;179432910 |
| N2A | 23415 | 70468;70469;70470 | chr2:178568185;178568184;178568183 | chr2:179432912;179432911;179432910 |
| N2B | 16918 | 50977;50978;50979 | chr2:178568185;178568184;178568183 | chr2:179432912;179432911;179432910 |
| Novex-1 | 17043 | 51352;51353;51354 | chr2:178568185;178568184;178568183 | chr2:179432912;179432911;179432910 |
| Novex-2 | 17110 | 51553;51554;51555 | chr2:178568185;178568184;178568183 | chr2:179432912;179432911;179432910 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/L | rs562762535  |
-0.371 | 0.001 | N | 0.177 | 0.036 | 0.388334884743 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 0 |
| V/L | rs562762535 |
-0.371 | 0.001 | N | 0.177 | 0.036 | 0.388334884743 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| V/L | rs562762535 |
-0.371 | 0.001 | N | 0.177 | 0.036 | 0.388334884743 | gnomAD-4.0.0 | 6.57333E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.07297E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2364 | likely_benign | 0.2413 | benign | -1.156 | Destabilizing | 0.089 | N | 0.457 | neutral | N | 0.465640658 | None | None | N |
| V/C | 0.741 | likely_pathogenic | 0.7095 | pathogenic | -0.977 | Destabilizing | 0.981 | D | 0.645 | neutral | None | None | None | None | N |
| V/D | 0.7145 | likely_pathogenic | 0.7104 | pathogenic | -0.768 | Destabilizing | 0.687 | D | 0.785 | deleterious | None | None | None | None | N |
| V/E | 0.4776 | ambiguous | 0.4746 | ambiguous | -0.803 | Destabilizing | 0.454 | N | 0.616 | neutral | N | 0.485960185 | None | None | N |
| V/F | 0.2437 | likely_benign | 0.2288 | benign | -0.942 | Destabilizing | 0.687 | D | 0.629 | neutral | None | None | None | None | N |
| V/G | 0.5105 | ambiguous | 0.5237 | ambiguous | -1.422 | Destabilizing | 0.624 | D | 0.688 | prob.delet. | N | 0.499090917 | None | None | N |
| V/H | 0.653 | likely_pathogenic | 0.6344 | pathogenic | -0.864 | Destabilizing | 0.944 | D | 0.815 | deleterious | None | None | None | None | N |
| V/I | 0.066 | likely_benign | 0.0633 | benign | -0.554 | Destabilizing | 0.001 | N | 0.237 | neutral | N | 0.463508166 | None | None | N |
| V/K | 0.3959 | ambiguous | 0.3928 | ambiguous | -0.972 | Destabilizing | 0.005 | N | 0.53 | neutral | None | None | None | None | N |
| V/L | 0.1565 | likely_benign | 0.1393 | benign | -0.554 | Destabilizing | 0.001 | N | 0.177 | neutral | N | 0.457504914 | None | None | N |
| V/M | 0.1382 | likely_benign | 0.1271 | benign | -0.5 | Destabilizing | 0.687 | D | 0.531 | neutral | None | None | None | None | N |
| V/N | 0.4711 | ambiguous | 0.4317 | ambiguous | -0.792 | Destabilizing | 0.687 | D | 0.787 | deleterious | None | None | None | None | N |
| V/P | 0.7007 | likely_pathogenic | 0.7019 | pathogenic | -0.718 | Destabilizing | 0.817 | D | 0.74 | deleterious | None | None | None | None | N |
| V/Q | 0.3983 | ambiguous | 0.3924 | ambiguous | -0.985 | Destabilizing | 0.687 | D | 0.739 | deleterious | None | None | None | None | N |
| V/R | 0.3734 | ambiguous | 0.3715 | ambiguous | -0.428 | Destabilizing | 0.524 | D | 0.777 | deleterious | None | None | None | None | N |
| V/S | 0.3586 | ambiguous | 0.3454 | ambiguous | -1.313 | Destabilizing | 0.687 | D | 0.651 | prob.neutral | None | None | None | None | N |
| V/T | 0.1359 | likely_benign | 0.1281 | benign | -1.236 | Destabilizing | 0.385 | N | 0.548 | neutral | None | None | None | None | N |
| V/W | 0.8564 | likely_pathogenic | 0.8527 | pathogenic | -1.056 | Destabilizing | 0.981 | D | 0.813 | deleterious | None | None | None | None | N |
| V/Y | 0.6353 | likely_pathogenic | 0.6035 | pathogenic | -0.771 | Destabilizing | 0.817 | D | 0.609 | 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.