Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20519 | 61780;61781;61782 | chr2:178590170;178590169;178590168 | chr2:179454897;179454896;179454895 |
| N2AB | 18878 | 56857;56858;56859 | chr2:178590170;178590169;178590168 | chr2:179454897;179454896;179454895 |
| N2A | 17951 | 54076;54077;54078 | chr2:178590170;178590169;178590168 | chr2:179454897;179454896;179454895 |
| N2B | 11454 | 34585;34586;34587 | chr2:178590170;178590169;178590168 | chr2:179454897;179454896;179454895 |
| Novex-1 | 11579 | 34960;34961;34962 | chr2:178590170;178590169;178590168 | chr2:179454897;179454896;179454895 |
| Novex-2 | 11646 | 35161;35162;35163 | chr2:178590170;178590169;178590168 | chr2:179454897;179454896;179454895 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs727504191  |
0.059 | 0.002 | N | 0.179 | 0.062 | 0.149567049428 | gnomAD-2.1.1 | 5.26E-05 | None | None | None | None | N | None | 0 | 3.20812E-04 | None | 0 | 0 | None | 3.3E-05 | None | 0 | 0 | 1.67392E-04 |
| R/Q | rs727504191 |
0.059 | 0.002 | N | 0.179 | 0.062 | 0.149567049428 | gnomAD-3.1.2 | 1.57845E-04 | None | None | None | None | N | None | 0 | 1.57336E-03 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs727504191 |
0.059 | 0.002 | N | 0.179 | 0.062 | 0.149567049428 | gnomAD-4.0.0 | 3.0393E-05 | None | None | None | None | N | None | 1.33611E-05 | 6.01544E-04 | None | 0 | 2.23324E-05 | None | 0 | 1.64799E-04 | 5.93636E-06 | 2.20405E-05 | 1.60303E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.1905 | likely_benign | 0.1793 | benign | -0.157 | Destabilizing | 0.007 | N | 0.219 | neutral | None | None | None | None | N |
| R/C | 0.1895 | likely_benign | 0.1825 | benign | -0.303 | Destabilizing | 0.864 | D | 0.282 | neutral | None | None | None | None | N |
| R/D | 0.401 | ambiguous | 0.3807 | ambiguous | -0.018 | Destabilizing | 0.016 | N | 0.248 | neutral | None | None | None | None | N |
| R/E | 0.2098 | likely_benign | 0.1968 | benign | 0.067 | Stabilizing | None | N | 0.141 | neutral | None | None | None | None | N |
| R/F | 0.4983 | ambiguous | 0.4698 | ambiguous | -0.265 | Destabilizing | 0.628 | D | 0.331 | neutral | None | None | None | None | N |
| R/G | 0.1179 | likely_benign | 0.1275 | benign | -0.389 | Destabilizing | 0.026 | N | 0.257 | neutral | N | 0.476088754 | None | None | N |
| R/H | 0.1163 | likely_benign | 0.1087 | benign | -0.84 | Destabilizing | 0.356 | N | 0.219 | neutral | None | None | None | None | N |
| R/I | 0.244 | likely_benign | 0.2477 | benign | 0.431 | Stabilizing | 0.136 | N | 0.396 | neutral | None | None | None | None | N |
| R/K | 0.0734 | likely_benign | 0.0644 | benign | -0.233 | Destabilizing | None | N | 0.131 | neutral | None | None | None | None | N |
| R/L | 0.1835 | likely_benign | 0.1773 | benign | 0.431 | Stabilizing | 0.058 | N | 0.287 | neutral | N | 0.462082093 | None | None | N |
| R/M | 0.2064 | likely_benign | 0.1906 | benign | -0.031 | Destabilizing | 0.356 | N | 0.262 | neutral | None | None | None | None | N |
| R/N | 0.3219 | likely_benign | 0.316 | benign | 0.032 | Stabilizing | None | N | 0.122 | neutral | None | None | None | None | N |
| R/P | 0.1934 | likely_benign | 0.169 | benign | 0.256 | Stabilizing | 0.232 | N | 0.394 | neutral | N | 0.437434365 | None | None | N |
| R/Q | 0.0855 | likely_benign | 0.0821 | benign | -0.064 | Destabilizing | 0.002 | N | 0.179 | neutral | N | 0.475779322 | None | None | N |
| R/S | 0.2525 | likely_benign | 0.2551 | benign | -0.419 | Destabilizing | 0.001 | N | 0.159 | neutral | None | None | None | None | N |
| R/T | 0.1359 | likely_benign | 0.1379 | benign | -0.182 | Destabilizing | 0.016 | N | 0.265 | neutral | None | None | None | None | N |
| R/V | 0.2741 | likely_benign | 0.2591 | benign | 0.256 | Stabilizing | 0.072 | N | 0.366 | neutral | None | None | None | None | N |
| R/W | 0.1879 | likely_benign | 0.1782 | benign | -0.225 | Destabilizing | 0.864 | D | 0.288 | neutral | None | None | None | None | N |
| R/Y | 0.3787 | ambiguous | 0.3535 | ambiguous | 0.158 | Stabilizing | 0.628 | D | 0.351 | 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.