Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29025 | 87298;87299;87300 | chr2:178558386;178558385;178558384 | chr2:179423113;179423112;179423111 |
| N2AB | 27384 | 82375;82376;82377 | chr2:178558386;178558385;178558384 | chr2:179423113;179423112;179423111 |
| N2A | 26457 | 79594;79595;79596 | chr2:178558386;178558385;178558384 | chr2:179423113;179423112;179423111 |
| N2B | 19960 | 60103;60104;60105 | chr2:178558386;178558385;178558384 | chr2:179423113;179423112;179423111 |
| Novex-1 | 20085 | 60478;60479;60480 | chr2:178558386;178558385;178558384 | chr2:179423113;179423112;179423111 |
| Novex-2 | 20152 | 60679;60680;60681 | chr2:178558386;178558385;178558384 | chr2:179423113;179423112;179423111 |
| 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/H | rs1702323691  |
None | 1.0 | N | 0.705 | 0.368 | 0.307648195649 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/H | rs1702323691 |
None | 1.0 | N | 0.705 | 0.368 | 0.307648195649 | gnomAD-4.0.0 | 2.56268E-06 | None | None | None | None | I | None | 3.38238E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.1511 | likely_benign | 0.1604 | benign | -0.669 | Destabilizing | 0.998 | D | 0.709 | prob.delet. | N | 0.455622189 | None | None | I |
| D/C | 0.6458 | likely_pathogenic | 0.6604 | pathogenic | -0.285 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | I |
| D/E | 0.1156 | likely_benign | 0.1224 | benign | -0.498 | Destabilizing | 0.4 | N | 0.228 | neutral | N | 0.396573885 | None | None | I |
| D/F | 0.5246 | ambiguous | 0.5575 | ambiguous | -0.21 | Destabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | I |
| D/G | 0.2557 | likely_benign | 0.2696 | benign | -0.957 | Destabilizing | 0.998 | D | 0.716 | prob.delet. | N | 0.517228008 | None | None | I |
| D/H | 0.3113 | likely_benign | 0.3267 | benign | -0.19 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | N | 0.509283315 | None | None | I |
| D/I | 0.2736 | likely_benign | 0.2895 | benign | 0.076 | Stabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | I |
| D/K | 0.3553 | ambiguous | 0.3676 | ambiguous | -0.155 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | I |
| D/L | 0.2926 | likely_benign | 0.3117 | benign | 0.076 | Stabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | I |
| D/M | 0.4807 | ambiguous | 0.5029 | ambiguous | 0.348 | Stabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | I |
| D/N | 0.1143 | likely_benign | 0.115 | benign | -0.632 | Destabilizing | 0.999 | D | 0.72 | prob.delet. | N | 0.515921286 | None | None | I |
| D/P | 0.5042 | ambiguous | 0.5144 | ambiguous | -0.15 | Destabilizing | 0.999 | D | 0.755 | deleterious | None | None | None | None | I |
| D/Q | 0.2826 | likely_benign | 0.3044 | benign | -0.538 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | I |
| D/R | 0.4424 | ambiguous | 0.4619 | ambiguous | 0.148 | Stabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | I |
| D/S | 0.1206 | likely_benign | 0.1271 | benign | -0.802 | Destabilizing | 0.998 | D | 0.684 | prob.neutral | None | None | None | None | I |
| D/T | 0.2312 | likely_benign | 0.2403 | benign | -0.565 | Destabilizing | 0.999 | D | 0.714 | prob.delet. | None | None | None | None | I |
| D/V | 0.1627 | likely_benign | 0.1731 | benign | -0.15 | Destabilizing | 0.999 | D | 0.759 | deleterious | N | 0.509283315 | None | None | I |
| D/W | 0.8925 | likely_pathogenic | 0.9065 | pathogenic | 0.07 | Stabilizing | 1.0 | D | 0.754 | deleterious | None | None | None | None | I |
| D/Y | 0.2512 | likely_benign | 0.265 | benign | 0.054 | Stabilizing | 1.0 | D | 0.747 | deleterious | N | 0.482155659 | 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.