Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27927 | 84004;84005;84006 | chr2:178562353;178562352;178562351 | chr2:179427080;179427079;179427078 |
| N2AB | 26286 | 79081;79082;79083 | chr2:178562353;178562352;178562351 | chr2:179427080;179427079;179427078 |
| N2A | 25359 | 76300;76301;76302 | chr2:178562353;178562352;178562351 | chr2:179427080;179427079;179427078 |
| N2B | 18862 | 56809;56810;56811 | chr2:178562353;178562352;178562351 | chr2:179427080;179427079;179427078 |
| Novex-1 | 18987 | 57184;57185;57186 | chr2:178562353;178562352;178562351 | chr2:179427080;179427079;179427078 |
| Novex-2 | 19054 | 57385;57386;57387 | chr2:178562353;178562352;178562351 | chr2:179427080;179427079;179427078 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/P | rs1164046049  |
None | 0.896 | N | 0.389 | 0.241 | 0.259761712551 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/P | rs1164046049 |
None | 0.896 | N | 0.389 | 0.241 | 0.259761712551 | gnomAD-4.0.0 | 3.10396E-06 | None | None | None | None | N | None | 6.68861E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/S | rs1271253201 |
-0.552 | 0.007 | N | 0.116 | 0.068 | 0.134241683229 | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.36E-05 | None | 0 | 0 | 0 |
| T/S | rs1271253201 |
-0.552 | 0.007 | N | 0.116 | 0.068 | 0.134241683229 | gnomAD-4.0.0 | 4.79454E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86658E-06 | 2.89051E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0774 | likely_benign | 0.0807 | benign | -0.694 | Destabilizing | 0.201 | N | 0.329 | neutral | N | 0.473882663 | None | None | N |
| T/C | 0.3747 | ambiguous | 0.3941 | ambiguous | -0.416 | Destabilizing | 0.012 | N | 0.263 | neutral | None | None | None | None | N |
| T/D | 0.4327 | ambiguous | 0.4729 | ambiguous | 0.385 | Stabilizing | 0.617 | D | 0.383 | neutral | None | None | None | None | N |
| T/E | 0.3238 | likely_benign | 0.353 | ambiguous | 0.341 | Stabilizing | 0.617 | D | 0.384 | neutral | None | None | None | None | N |
| T/F | 0.2335 | likely_benign | 0.2618 | benign | -1.111 | Destabilizing | 0.92 | D | 0.451 | neutral | None | None | None | None | N |
| T/G | 0.2387 | likely_benign | 0.2564 | benign | -0.86 | Destabilizing | 0.447 | N | 0.367 | neutral | None | None | None | None | N |
| T/H | 0.2253 | likely_benign | 0.2414 | benign | -1.051 | Destabilizing | 0.977 | D | 0.437 | neutral | None | None | None | None | N |
| T/I | 0.1282 | likely_benign | 0.145 | benign | -0.367 | Destabilizing | 0.81 | D | 0.361 | neutral | N | 0.454374182 | None | None | N |
| T/K | 0.194 | likely_benign | 0.209 | benign | -0.367 | Destabilizing | 0.447 | N | 0.383 | neutral | None | None | None | None | N |
| T/L | 0.0844 | likely_benign | 0.0872 | benign | -0.367 | Destabilizing | 0.447 | N | 0.315 | neutral | None | None | None | None | N |
| T/M | 0.0865 | likely_benign | 0.0916 | benign | -0.206 | Destabilizing | 0.972 | D | 0.375 | neutral | None | None | None | None | N |
| T/N | 0.121 | likely_benign | 0.1286 | benign | -0.244 | Destabilizing | 0.379 | N | 0.345 | neutral | N | 0.451603236 | None | None | N |
| T/P | 0.1869 | likely_benign | 0.2288 | benign | -0.447 | Destabilizing | 0.896 | D | 0.389 | neutral | N | 0.503474851 | None | None | N |
| T/Q | 0.2054 | likely_benign | 0.2202 | benign | -0.408 | Destabilizing | 0.85 | D | 0.375 | neutral | None | None | None | None | N |
| T/R | 0.1665 | likely_benign | 0.1836 | benign | -0.116 | Destabilizing | 0.85 | D | 0.393 | neutral | None | None | None | None | N |
| T/S | 0.1043 | likely_benign | 0.1077 | benign | -0.546 | Destabilizing | 0.007 | N | 0.116 | neutral | N | 0.437249859 | None | None | N |
| T/V | 0.1041 | likely_benign | 0.1127 | benign | -0.447 | Destabilizing | 0.617 | D | 0.283 | neutral | None | None | None | None | N |
| T/W | 0.5724 | likely_pathogenic | 0.6107 | pathogenic | -1.062 | Destabilizing | 0.992 | D | 0.506 | neutral | None | None | None | None | N |
| T/Y | 0.2711 | likely_benign | 0.2946 | benign | -0.794 | Destabilizing | 0.972 | D | 0.449 | 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.