Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23965 | 72118;72119;72120 | chr2:178574239;178574238;178574237 | chr2:179438966;179438965;179438964 |
| N2AB | 22324 | 67195;67196;67197 | chr2:178574239;178574238;178574237 | chr2:179438966;179438965;179438964 |
| N2A | 21397 | 64414;64415;64416 | chr2:178574239;178574238;178574237 | chr2:179438966;179438965;179438964 |
| N2B | 14900 | 44923;44924;44925 | chr2:178574239;178574238;178574237 | chr2:179438966;179438965;179438964 |
| Novex-1 | 15025 | 45298;45299;45300 | chr2:178574239;178574238;178574237 | chr2:179438966;179438965;179438964 |
| Novex-2 | 15092 | 45499;45500;45501 | chr2:178574239;178574238;178574237 | chr2:179438966;179438965;179438964 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs772655984  |
-0.564 | 0.198 | N | 0.148 | 0.033 | 0.271763555656 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| D/E | rs772655984 |
-0.564 | 0.198 | N | 0.148 | 0.033 | 0.271763555656 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/E | rs772655984 |
-0.564 | 0.198 | N | 0.148 | 0.033 | 0.271763555656 | gnomAD-4.0.0 | 3.71956E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.2392E-06 | 1.09825E-05 | 0 |
| D/Y | rs1709278719 |
None | 1.0 | N | 0.753 | 0.575 | 0.764077007804 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.41E-05 | 0 | 1.47E-05 | 0 | 0 |
| D/Y | rs1709278719 |
None | 1.0 | N | 0.753 | 0.575 | 0.764077007804 | gnomAD-4.0.0 | 2.47968E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.5627E-05 | 0 | 2.54357E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.3847 | ambiguous | 0.3904 | ambiguous | -0.548 | Destabilizing | 0.978 | D | 0.551 | neutral | N | 0.465341624 | None | None | N |
| D/C | 0.8364 | likely_pathogenic | 0.8344 | pathogenic | -0.264 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| D/E | 0.2195 | likely_benign | 0.224 | benign | -0.676 | Destabilizing | 0.198 | N | 0.148 | neutral | N | 0.40996447 | None | None | N |
| D/F | 0.8079 | likely_pathogenic | 0.8189 | pathogenic | -0.011 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | N |
| D/G | 0.4704 | ambiguous | 0.4841 | ambiguous | -0.939 | Destabilizing | 0.989 | D | 0.537 | neutral | N | 0.466355582 | None | None | N |
| D/H | 0.6147 | likely_pathogenic | 0.5997 | pathogenic | -0.374 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | N | 0.497626568 | None | None | N |
| D/I | 0.5671 | likely_pathogenic | 0.5696 | pathogenic | 0.499 | Stabilizing | 0.999 | D | 0.784 | deleterious | None | None | None | None | N |
| D/K | 0.7235 | likely_pathogenic | 0.7007 | pathogenic | -0.431 | Destabilizing | 0.983 | D | 0.541 | neutral | None | None | None | None | N |
| D/L | 0.5673 | likely_pathogenic | 0.576 | pathogenic | 0.499 | Stabilizing | 0.998 | D | 0.765 | deleterious | None | None | None | None | N |
| D/M | 0.7873 | likely_pathogenic | 0.7937 | pathogenic | 0.945 | Stabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| D/N | 0.2239 | likely_benign | 0.2326 | benign | -0.93 | Destabilizing | 0.989 | D | 0.484 | neutral | N | 0.465341624 | None | None | N |
| D/P | 0.7813 | likely_pathogenic | 0.7625 | pathogenic | 0.176 | Stabilizing | 0.999 | D | 0.733 | prob.delet. | None | None | None | None | N |
| D/Q | 0.5928 | likely_pathogenic | 0.5748 | pathogenic | -0.755 | Destabilizing | 0.995 | D | 0.565 | neutral | None | None | None | None | N |
| D/R | 0.764 | likely_pathogenic | 0.7445 | pathogenic | -0.273 | Destabilizing | 0.995 | D | 0.739 | prob.delet. | None | None | None | None | N |
| D/S | 0.3183 | likely_benign | 0.3261 | benign | -1.243 | Destabilizing | 0.983 | D | 0.415 | neutral | None | None | None | None | N |
| D/T | 0.5382 | ambiguous | 0.5355 | ambiguous | -0.911 | Destabilizing | 0.998 | D | 0.617 | neutral | None | None | None | None | N |
| D/V | 0.3907 | ambiguous | 0.3923 | ambiguous | 0.176 | Stabilizing | 0.997 | D | 0.757 | deleterious | N | 0.469976433 | None | None | N |
| D/W | 0.9592 | likely_pathogenic | 0.9604 | pathogenic | 0.182 | Stabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| D/Y | 0.4349 | ambiguous | 0.4358 | ambiguous | 0.245 | Stabilizing | 1.0 | D | 0.753 | deleterious | N | 0.516580197 | 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.