Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1603 | 5032;5033;5034 | chr2:178777156;178777155;178777154 | chr2:179641883;179641882;179641881 |
| N2AB | 1603 | 5032;5033;5034 | chr2:178777156;178777155;178777154 | chr2:179641883;179641882;179641881 |
| N2A | 1603 | 5032;5033;5034 | chr2:178777156;178777155;178777154 | chr2:179641883;179641882;179641881 |
| N2B | 1557 | 4894;4895;4896 | chr2:178777156;178777155;178777154 | chr2:179641883;179641882;179641881 |
| Novex-1 | 1557 | 4894;4895;4896 | chr2:178777156;178777155;178777154 | chr2:179641883;179641882;179641881 |
| Novex-2 | 1557 | 4894;4895;4896 | chr2:178777156;178777155;178777154 | chr2:179641883;179641882;179641881 |
| Novex-3 | 1603 | 5032;5033;5034 | chr2:178777156;178777155;178777154 | chr2:179641883;179641882;179641881 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/N | rs764249850  |
-0.496 | None | N | 0.095 | 0.099 | 0.166414681773 | gnomAD-2.1.1 | 7.96E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.08873E-04 | None | 0 | None | 0 | 0 | 0 |
| K/N | rs764249850 |
-0.496 | None | N | 0.095 | 0.099 | 0.166414681773 | gnomAD-4.0.0 | 1.5907E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77346E-05 | None | 0 | 0 | 0 | 0 | 0 |
| K/Q | rs754087999 |
-0.399 | 0.055 | N | 0.211 | 0.194 | 0.251116650651 | gnomAD-2.1.1 | 2.39E-05 | None | None | None | None | N | None | 0 | 1.15647E-04 | None | 0 | 0 | None | 0 | None | 0 | 1.76E-05 | 0 |
| K/Q | rs754087999 |
-0.399 | 0.055 | N | 0.211 | 0.194 | 0.251116650651 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| K/Q | rs754087999 |
-0.399 | 0.055 | N | 0.211 | 0.194 | 0.251116650651 | gnomAD-4.0.0 | 1.67287E-05 | None | None | None | None | N | None | 0 | 4.99967E-05 | None | 0 | 0 | None | 0 | 0 | 1.94916E-05 | 1.09784E-05 | 0 |
| K/T | None | None | 0.055 | N | 0.327 | 0.251 | 0.280181792013 | gnomAD-4.0.0 | 1.59069E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85678E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.2078 | likely_benign | 0.1876 | benign | -0.25 | Destabilizing | 0.031 | N | 0.321 | neutral | None | None | None | None | N |
| K/C | 0.5717 | likely_pathogenic | 0.5142 | ambiguous | -0.465 | Destabilizing | 0.864 | D | 0.346 | neutral | None | None | None | None | N |
| K/D | 0.333 | likely_benign | 0.2979 | benign | 0.151 | Stabilizing | 0.016 | N | 0.315 | neutral | None | None | None | None | N |
| K/E | 0.1528 | likely_benign | 0.1386 | benign | 0.24 | Stabilizing | 0.012 | N | 0.272 | neutral | N | 0.440010192 | None | None | N |
| K/F | 0.6605 | likely_pathogenic | 0.608 | pathogenic | -0.072 | Destabilizing | 0.356 | N | 0.364 | neutral | None | None | None | None | N |
| K/G | 0.2093 | likely_benign | 0.1866 | benign | -0.561 | Destabilizing | 0.016 | N | 0.356 | neutral | None | None | None | None | N |
| K/H | 0.1733 | likely_benign | 0.1647 | benign | -0.791 | Destabilizing | None | N | 0.131 | neutral | None | None | None | None | N |
| K/I | 0.3765 | ambiguous | 0.326 | benign | 0.528 | Stabilizing | 0.295 | N | 0.388 | neutral | N | 0.503643569 | None | None | N |
| K/L | 0.2727 | likely_benign | 0.2364 | benign | 0.528 | Stabilizing | 0.072 | N | 0.366 | neutral | None | None | None | None | N |
| K/M | 0.2282 | likely_benign | 0.2027 | benign | 0.129 | Stabilizing | 0.628 | D | 0.343 | neutral | None | None | None | None | N |
| K/N | 0.2026 | likely_benign | 0.1776 | benign | -0.187 | Destabilizing | None | N | 0.095 | neutral | N | 0.434388127 | None | None | N |
| K/P | 0.6642 | likely_pathogenic | 0.5909 | pathogenic | 0.299 | Stabilizing | 0.136 | N | 0.385 | neutral | None | None | None | None | N |
| K/Q | 0.0977 | likely_benign | 0.0941 | benign | -0.211 | Destabilizing | 0.055 | N | 0.211 | neutral | N | 0.5004317 | None | None | N |
| K/R | 0.0626 | likely_benign | 0.0636 | benign | -0.352 | Destabilizing | None | N | 0.089 | neutral | N | 0.382667153 | None | None | N |
| K/S | 0.224 | likely_benign | 0.1985 | benign | -0.754 | Destabilizing | 0.016 | N | 0.238 | neutral | None | None | None | None | N |
| K/T | 0.155 | likely_benign | 0.14 | benign | -0.471 | Destabilizing | 0.055 | N | 0.327 | neutral | N | 0.492090289 | None | None | N |
| K/V | 0.3109 | likely_benign | 0.2752 | benign | 0.299 | Stabilizing | 0.072 | N | 0.399 | neutral | None | None | None | None | N |
| K/W | 0.5828 | likely_pathogenic | 0.5458 | ambiguous | -0.034 | Destabilizing | 0.864 | D | 0.361 | neutral | None | None | None | None | N |
| K/Y | 0.4587 | ambiguous | 0.4131 | ambiguous | 0.275 | Stabilizing | 0.072 | N | 0.387 | 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.