Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15005 | 45238;45239;45240 | chr2:178621909;178621908;178621907 | chr2:179486636;179486635;179486634 |
| N2AB | 13364 | 40315;40316;40317 | chr2:178621909;178621908;178621907 | chr2:179486636;179486635;179486634 |
| N2A | 12437 | 37534;37535;37536 | chr2:178621909;178621908;178621907 | chr2:179486636;179486635;179486634 |
| N2B | 5940 | 18043;18044;18045 | chr2:178621909;178621908;178621907 | chr2:179486636;179486635;179486634 |
| Novex-1 | 6065 | 18418;18419;18420 | chr2:178621909;178621908;178621907 | chr2:179486636;179486635;179486634 |
| Novex-2 | 6132 | 18619;18620;18621 | chr2:178621909;178621908;178621907 | chr2:179486636;179486635;179486634 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/P | rs369992659  |
-0.318 | 0.963 | N | 0.347 | 0.468 | None | gnomAD-2.1.1 | 3.23E-05 | None | None | None | None | I | None | 3.31263E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.84E-06 | 0 |
| L/P | rs369992659 |
-0.318 | 0.963 | N | 0.347 | 0.468 | None | gnomAD-3.1.2 | 1.25016E-04 | None | None | None | None | I | None | 4.34468E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/P | rs369992659 |
-0.318 | 0.963 | N | 0.347 | 0.468 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| L/P | rs369992659 |
-0.318 | 0.963 | N | 0.347 | 0.468 | None | gnomAD-4.0.0 | 1.73674E-05 | None | None | None | None | I | None | 3.20239E-04 | 0 | None | 0 | 0 | None | 1.56367E-05 | 0 | 8.48176E-07 | 0 | 3.20605E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.2074 | likely_benign | 0.2264 | benign | -0.389 | Destabilizing | 0.25 | N | 0.243 | neutral | None | None | None | None | I |
| L/C | 0.6351 | likely_pathogenic | 0.6815 | pathogenic | -0.402 | Destabilizing | 0.977 | D | 0.256 | neutral | None | None | None | None | I |
| L/D | 0.6685 | likely_pathogenic | 0.6918 | pathogenic | -0.243 | Destabilizing | 0.972 | D | 0.368 | neutral | None | None | None | None | I |
| L/E | 0.3655 | ambiguous | 0.3748 | ambiguous | -0.35 | Destabilizing | 0.92 | D | 0.355 | neutral | None | None | None | None | I |
| L/F | 0.1471 | likely_benign | 0.1562 | benign | -0.569 | Destabilizing | 0.001 | N | 0.125 | neutral | None | None | None | None | I |
| L/G | 0.4828 | ambiguous | 0.5158 | ambiguous | -0.524 | Destabilizing | 0.766 | D | 0.373 | neutral | None | None | None | None | I |
| L/H | 0.2395 | likely_benign | 0.2622 | benign | 0.031 | Stabilizing | 0.992 | D | 0.338 | neutral | None | None | None | None | I |
| L/I | 0.1123 | likely_benign | 0.1126 | benign | -0.161 | Destabilizing | 0.103 | N | 0.273 | neutral | None | None | None | None | I |
| L/K | 0.2246 | likely_benign | 0.2485 | benign | -0.194 | Destabilizing | 0.92 | D | 0.326 | neutral | None | None | None | None | I |
| L/M | 0.1392 | likely_benign | 0.1442 | benign | -0.273 | Destabilizing | 0.81 | D | 0.273 | neutral | N | 0.455481347 | None | None | I |
| L/N | 0.4168 | ambiguous | 0.4577 | ambiguous | 0.102 | Stabilizing | 0.972 | D | 0.351 | neutral | None | None | None | None | I |
| L/P | 0.1491 | likely_benign | 0.1516 | benign | -0.205 | Destabilizing | 0.963 | D | 0.347 | neutral | N | 0.424754471 | None | None | I |
| L/Q | 0.1542 | likely_benign | 0.159 | benign | -0.14 | Destabilizing | 0.963 | D | 0.318 | neutral | N | 0.455681995 | None | None | I |
| L/R | 0.1654 | likely_benign | 0.1782 | benign | 0.315 | Stabilizing | 0.896 | D | 0.331 | neutral | N | 0.449311925 | None | None | I |
| L/S | 0.2701 | likely_benign | 0.2881 | benign | -0.27 | Destabilizing | 0.617 | D | 0.322 | neutral | None | None | None | None | I |
| L/T | 0.2124 | likely_benign | 0.2304 | benign | -0.275 | Destabilizing | 0.617 | D | 0.241 | neutral | None | None | None | None | I |
| L/V | 0.1192 | likely_benign | 0.1213 | benign | -0.205 | Destabilizing | 0.002 | N | 0.163 | neutral | N | 0.449291507 | None | None | I |
| L/W | 0.2593 | likely_benign | 0.2573 | benign | -0.612 | Destabilizing | 0.992 | D | 0.324 | neutral | None | None | None | None | I |
| L/Y | 0.3683 | ambiguous | 0.417 | ambiguous | -0.336 | Destabilizing | 0.447 | N | 0.242 | neutral | None | None | None | None | I |
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.