Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3426 | 10501;10502;10503 | chr2:178759011;178759010;178759009 | chr2:179623738;179623737;179623736 |
| N2AB | 3426 | 10501;10502;10503 | chr2:178759011;178759010;178759009 | chr2:179623738;179623737;179623736 |
| N2A | 3426 | 10501;10502;10503 | chr2:178759011;178759010;178759009 | chr2:179623738;179623737;179623736 |
| N2B | 3380 | 10363;10364;10365 | chr2:178759011;178759010;178759009 | chr2:179623738;179623737;179623736 |
| Novex-1 | 3380 | 10363;10364;10365 | chr2:178759011;178759010;178759009 | chr2:179623738;179623737;179623736 |
| Novex-2 | 3380 | 10363;10364;10365 | chr2:178759011;178759010;178759009 | chr2:179623738;179623737;179623736 |
| Novex-3 | 3426 | 10501;10502;10503 | chr2:178759011;178759010;178759009 | chr2:179623738;179623737;179623736 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/L | rs2088194295  |
None | 0.811 | D | 0.627 | 0.398 | 0.767801976584 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06954E-04 | 0 |
| S/L | rs2088194295 |
None | 0.811 | D | 0.627 | 0.398 | 0.767801976584 | gnomAD-4.0.0 | 6.57125E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.06954E-04 | 0 |
| S/P | None | None | 0.984 | D | 0.705 | 0.474 | 0.522344865107 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 1.94099E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0946 | likely_benign | 0.0968 | benign | -0.481 | Destabilizing | 0.64 | D | 0.453 | neutral | D | 0.54393467 | None | None | I |
| S/C | 0.1641 | likely_benign | 0.1503 | benign | -0.393 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | I |
| S/D | 0.5244 | ambiguous | 0.6355 | pathogenic | 0.484 | Stabilizing | 0.919 | D | 0.499 | neutral | None | None | None | None | I |
| S/E | 0.4795 | ambiguous | 0.6254 | pathogenic | 0.441 | Stabilizing | 0.919 | D | 0.501 | neutral | None | None | None | None | I |
| S/F | 0.1878 | likely_benign | 0.205 | benign | -0.862 | Destabilizing | 0.976 | D | 0.742 | deleterious | None | None | None | None | I |
| S/G | 0.1674 | likely_benign | 0.1907 | benign | -0.661 | Destabilizing | 0.919 | D | 0.481 | neutral | None | None | None | None | I |
| S/H | 0.3088 | likely_benign | 0.4169 | ambiguous | -1.063 | Destabilizing | 0.999 | D | 0.675 | neutral | None | None | None | None | I |
| S/I | 0.1796 | likely_benign | 0.2104 | benign | -0.129 | Destabilizing | 0.952 | D | 0.654 | neutral | None | None | None | None | I |
| S/K | 0.5821 | likely_pathogenic | 0.7497 | pathogenic | -0.373 | Destabilizing | 0.919 | D | 0.505 | neutral | None | None | None | None | I |
| S/L | 0.1266 | likely_benign | 0.1267 | benign | -0.129 | Destabilizing | 0.811 | D | 0.627 | neutral | D | 0.575157868 | None | None | I |
| S/M | 0.2429 | likely_benign | 0.2589 | benign | -0.091 | Destabilizing | 0.702 | D | 0.459 | neutral | None | None | None | None | I |
| S/N | 0.1845 | likely_benign | 0.2416 | benign | -0.239 | Destabilizing | 0.919 | D | 0.515 | neutral | None | None | None | None | I |
| S/P | 0.747 | likely_pathogenic | 0.8147 | pathogenic | -0.214 | Destabilizing | 0.984 | D | 0.705 | prob.neutral | D | 0.668518718 | None | None | I |
| S/Q | 0.4286 | ambiguous | 0.5839 | pathogenic | -0.382 | Destabilizing | 0.988 | D | 0.548 | neutral | None | None | None | None | I |
| S/R | 0.4359 | ambiguous | 0.6181 | pathogenic | -0.262 | Destabilizing | 0.988 | D | 0.703 | prob.neutral | None | None | None | None | I |
| S/T | 0.0727 | likely_benign | 0.0784 | benign | -0.338 | Destabilizing | 0.103 | N | 0.293 | neutral | N | 0.492753553 | None | None | I |
| S/V | 0.1909 | likely_benign | 0.2131 | benign | -0.214 | Destabilizing | 0.851 | D | 0.607 | neutral | None | None | None | None | I |
| S/W | 0.4037 | ambiguous | 0.4329 | ambiguous | -0.849 | Destabilizing | 0.999 | D | 0.755 | deleterious | None | None | None | None | I |
| S/Y | 0.1916 | likely_benign | 0.2112 | benign | -0.562 | Destabilizing | 0.996 | D | 0.745 | deleterious | 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.