Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14636 | 44131;44132;44133 | chr2:178631142;178631141;178631140 | chr2:179495869;179495868;179495867 |
| N2AB | 12995 | 39208;39209;39210 | chr2:178631142;178631141;178631140 | chr2:179495869;179495868;179495867 |
| N2A | 12068 | 36427;36428;36429 | chr2:178631142;178631141;178631140 | chr2:179495869;179495868;179495867 |
| N2B | 5571 | 16936;16937;16938 | chr2:178631142;178631141;178631140 | chr2:179495869;179495868;179495867 |
| Novex-1 | 5696 | 17311;17312;17313 | chr2:178631142;178631141;178631140 | chr2:179495869;179495868;179495867 |
| Novex-2 | 5763 | 17512;17513;17514 | chr2:178631142;178631141;178631140 | chr2:179495869;179495868;179495867 |
| 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 | rs1469705451  |
0.104 | 0.767 | N | 0.274 | 0.101 | 0.393159880135 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.24643E-04 | None | 0 | None | 0 | 0 | 0 |
| D/E | rs1469705451 |
0.104 | 0.767 | N | 0.274 | 0.101 | 0.393159880135 | gnomAD-4.0.0 | 6.36916E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.11297E-04 | None | 0 | 0 | 0 | 0 | 0 |
| D/H | None | None | 1.0 | D | 0.684 | 0.508 | 0.577797438266 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.21507E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1963 | likely_benign | 0.2039 | benign | -0.041 | Destabilizing | 0.999 | D | 0.655 | neutral | D | 0.574868101 | None | None | N |
| D/C | 0.7637 | likely_pathogenic | 0.7752 | pathogenic | 0.087 | Stabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| D/E | 0.2128 | likely_benign | 0.2057 | benign | -0.212 | Destabilizing | 0.767 | D | 0.274 | neutral | N | 0.491104061 | None | None | N |
| D/F | 0.6347 | likely_pathogenic | 0.6402 | pathogenic | -0.094 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| D/G | 0.2556 | likely_benign | 0.2824 | benign | -0.192 | Destabilizing | 0.998 | D | 0.653 | neutral | N | 0.506573007 | None | None | N |
| D/H | 0.3985 | ambiguous | 0.3894 | ambiguous | 0.283 | Stabilizing | 1.0 | D | 0.684 | prob.neutral | D | 0.640890232 | None | None | N |
| D/I | 0.375 | ambiguous | 0.3725 | ambiguous | 0.293 | Stabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| D/K | 0.4399 | ambiguous | 0.4676 | ambiguous | 0.506 | Stabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | N |
| D/L | 0.4921 | ambiguous | 0.5001 | ambiguous | 0.293 | Stabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| D/M | 0.7107 | likely_pathogenic | 0.7065 | pathogenic | 0.267 | Stabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| D/N | 0.1093 | likely_benign | 0.1169 | benign | 0.281 | Stabilizing | 0.999 | D | 0.628 | neutral | N | 0.508350679 | None | None | N |
| D/P | 0.9122 | likely_pathogenic | 0.9317 | pathogenic | 0.203 | Stabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| D/Q | 0.4576 | ambiguous | 0.4568 | ambiguous | 0.289 | Stabilizing | 0.999 | D | 0.667 | neutral | None | None | None | None | N |
| D/R | 0.4944 | ambiguous | 0.5188 | ambiguous | 0.678 | Stabilizing | 0.999 | D | 0.725 | prob.delet. | None | None | None | None | N |
| D/S | 0.1481 | likely_benign | 0.1579 | benign | 0.171 | Stabilizing | 0.997 | D | 0.566 | neutral | None | None | None | None | N |
| D/T | 0.3046 | likely_benign | 0.3224 | benign | 0.29 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| D/V | 0.2085 | likely_benign | 0.213 | benign | 0.203 | Stabilizing | 0.999 | D | 0.743 | deleterious | D | 0.585730636 | None | None | N |
| D/W | 0.905 | likely_pathogenic | 0.9112 | pathogenic | -0.024 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | N |
| D/Y | 0.2466 | likely_benign | 0.2511 | benign | 0.143 | Stabilizing | 1.0 | D | 0.729 | prob.delet. | D | 0.746690911 | 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.