Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14612 | 44059;44060;44061 | chr2:178631214;178631213;178631212 | chr2:179495941;179495940;179495939 |
| N2AB | 12971 | 39136;39137;39138 | chr2:178631214;178631213;178631212 | chr2:179495941;179495940;179495939 |
| N2A | 12044 | 36355;36356;36357 | chr2:178631214;178631213;178631212 | chr2:179495941;179495940;179495939 |
| N2B | 5547 | 16864;16865;16866 | chr2:178631214;178631213;178631212 | chr2:179495941;179495940;179495939 |
| Novex-1 | 5672 | 17239;17240;17241 | chr2:178631214;178631213;178631212 | chr2:179495941;179495940;179495939 |
| Novex-2 | 5739 | 17440;17441;17442 | chr2:178631214;178631213;178631212 | chr2:179495941;179495940;179495939 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/E | rs965521601  |
-0.634 | 0.002 | N | 0.331 | 0.183 | 0.440182696023 | gnomAD-2.1.1 | 6.38E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.29685E-04 | 0 |
| A/E | rs965521601 |
-0.634 | 0.002 | N | 0.331 | 0.183 | 0.440182696023 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| A/E | rs965521601 |
-0.634 | 0.002 | N | 0.331 | 0.183 | 0.440182696023 | gnomAD-4.0.0 | 1.67398E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.28904E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7793 | likely_pathogenic | 0.7189 | pathogenic | -0.806 | Destabilizing | 0.968 | D | 0.565 | neutral | None | None | None | None | N |
| A/D | 0.238 | likely_benign | 0.1952 | benign | -0.577 | Destabilizing | 0.157 | N | 0.618 | neutral | None | None | None | None | N |
| A/E | 0.1946 | likely_benign | 0.1627 | benign | -0.711 | Destabilizing | 0.002 | N | 0.331 | neutral | N | 0.47608488 | None | None | N |
| A/F | 0.535 | ambiguous | 0.4578 | ambiguous | -1.085 | Destabilizing | 0.89 | D | 0.678 | prob.neutral | None | None | None | None | N |
| A/G | 0.1693 | likely_benign | 0.1557 | benign | -0.672 | Destabilizing | 0.22 | N | 0.531 | neutral | N | 0.513138782 | None | None | N |
| A/H | 0.6076 | likely_pathogenic | 0.5263 | ambiguous | -0.717 | Destabilizing | 0.909 | D | 0.677 | prob.neutral | None | None | None | None | N |
| A/I | 0.3691 | ambiguous | 0.3015 | benign | -0.47 | Destabilizing | 0.726 | D | 0.545 | neutral | None | None | None | None | N |
| A/K | 0.4065 | ambiguous | 0.3607 | ambiguous | -0.762 | Destabilizing | 0.157 | N | 0.529 | neutral | None | None | None | None | N |
| A/L | 0.2705 | likely_benign | 0.2341 | benign | -0.47 | Destabilizing | 0.272 | N | 0.529 | neutral | None | None | None | None | N |
| A/M | 0.3462 | ambiguous | 0.2998 | benign | -0.344 | Destabilizing | 0.968 | D | 0.573 | neutral | None | None | None | None | N |
| A/N | 0.3042 | likely_benign | 0.2597 | benign | -0.422 | Destabilizing | 0.567 | D | 0.65 | neutral | None | None | None | None | N |
| A/P | 0.1287 | likely_benign | 0.1069 | benign | -0.465 | Destabilizing | 0.002 | N | 0.33 | neutral | N | 0.480482198 | None | None | N |
| A/Q | 0.3507 | ambiguous | 0.3082 | benign | -0.719 | Destabilizing | 0.396 | N | 0.549 | neutral | None | None | None | None | N |
| A/R | 0.3949 | ambiguous | 0.3746 | ambiguous | -0.31 | Destabilizing | 0.567 | D | 0.548 | neutral | None | None | None | None | N |
| A/S | 0.1132 | likely_benign | 0.1032 | benign | -0.703 | Destabilizing | 0.011 | N | 0.289 | neutral | N | 0.48597615 | None | None | N |
| A/T | 0.1138 | likely_benign | 0.1038 | benign | -0.756 | Destabilizing | 0.124 | N | 0.532 | neutral | N | 0.508144633 | None | None | N |
| A/V | 0.178 | likely_benign | 0.1523 | benign | -0.465 | Destabilizing | 0.22 | N | 0.521 | neutral | N | 0.503856826 | None | None | N |
| A/W | 0.8338 | likely_pathogenic | 0.7886 | pathogenic | -1.23 | Destabilizing | 0.968 | D | 0.72 | prob.delet. | None | None | None | None | N |
| A/Y | 0.6345 | likely_pathogenic | 0.5716 | pathogenic | -0.872 | Destabilizing | 0.89 | D | 0.679 | 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.