Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19439 | 58540;58541;58542 | chr2:178594078;178594077;178594076 | chr2:179458805;179458804;179458803 |
| N2AB | 17798 | 53617;53618;53619 | chr2:178594078;178594077;178594076 | chr2:179458805;179458804;179458803 |
| N2A | 16871 | 50836;50837;50838 | chr2:178594078;178594077;178594076 | chr2:179458805;179458804;179458803 |
| N2B | 10374 | 31345;31346;31347 | chr2:178594078;178594077;178594076 | chr2:179458805;179458804;179458803 |
| Novex-1 | 10499 | 31720;31721;31722 | chr2:178594078;178594077;178594076 | chr2:179458805;179458804;179458803 |
| Novex-2 | 10566 | 31921;31922;31923 | chr2:178594078;178594077;178594076 | chr2:179458805;179458804;179458803 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | rs368847168  |
0.023 | None | N | 0.184 | 0.069 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/A | rs368847168 |
0.023 | None | N | 0.184 | 0.069 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/A | rs368847168 |
0.023 | None | N | 0.184 | 0.069 | None | gnomAD-4.0.0 | 6.57869E-06 | None | None | None | None | N | None | 2.41488E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/L | None | None | 0.062 | N | 0.347 | 0.206 | 0.195762928549 | gnomAD-4.0.0 | 4.80129E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.25001E-06 | 0 | 0 |
| P/S | rs368847168 |
-0.131 | 0.027 | N | 0.323 | 0.067 | None | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4E-05 | 1.56E-05 | 0 |
| P/S | rs368847168 |
-0.131 | 0.027 | N | 0.323 | 0.067 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/S | rs368847168 |
-0.131 | 0.027 | N | 0.323 | 0.067 | None | gnomAD-4.0.0 | 4.33893E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.56235E-05 | 0 | 4.2385E-06 | 1.0981E-05 | 0 |
| P/T | None | -0.15 | 0.002 | N | 0.246 | 0.126 | 0.17948927462 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14837E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/T | None | -0.15 | 0.002 | N | 0.246 | 0.126 | 0.17948927462 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/T | None | -0.15 | 0.002 | N | 0.246 | 0.126 | 0.17948927462 | gnomAD-4.0.0 | 6.57869E-06 | None | None | None | None | N | None | 2.41488E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.057 | likely_benign | 0.0561 | benign | -0.419 | Destabilizing | None | N | 0.184 | neutral | N | 0.462153011 | None | None | N |
| P/C | 0.4347 | ambiguous | 0.4579 | ambiguous | -0.714 | Destabilizing | 0.824 | D | 0.377 | neutral | None | None | None | None | N |
| P/D | 0.2023 | likely_benign | 0.2337 | benign | -0.326 | Destabilizing | 0.149 | N | 0.328 | neutral | None | None | None | None | N |
| P/E | 0.1597 | likely_benign | 0.1806 | benign | -0.429 | Destabilizing | 0.149 | N | 0.33 | neutral | None | None | None | None | N |
| P/F | 0.3944 | ambiguous | 0.4037 | ambiguous | -0.627 | Destabilizing | 0.555 | D | 0.367 | neutral | None | None | None | None | N |
| P/G | 0.2029 | likely_benign | 0.2138 | benign | -0.532 | Destabilizing | 0.081 | N | 0.333 | neutral | None | None | None | None | N |
| P/H | 0.169 | likely_benign | 0.1875 | benign | 0.003 | Stabilizing | 0.935 | D | 0.355 | neutral | None | None | None | None | N |
| P/I | 0.2219 | likely_benign | 0.2176 | benign | -0.263 | Destabilizing | 0.38 | N | 0.369 | neutral | None | None | None | None | N |
| P/K | 0.2155 | likely_benign | 0.2594 | benign | -0.434 | Destabilizing | 0.149 | N | 0.323 | neutral | None | None | None | None | N |
| P/L | 0.0927 | likely_benign | 0.0977 | benign | -0.263 | Destabilizing | 0.062 | N | 0.347 | neutral | N | 0.467156186 | None | None | N |
| P/M | 0.2055 | likely_benign | 0.2074 | benign | -0.488 | Destabilizing | 0.824 | D | 0.345 | neutral | None | None | None | None | N |
| P/N | 0.1877 | likely_benign | 0.1897 | benign | -0.246 | Destabilizing | 0.555 | D | 0.347 | neutral | None | None | None | None | N |
| P/Q | 0.127 | likely_benign | 0.1401 | benign | -0.459 | Destabilizing | 0.484 | N | 0.279 | neutral | N | 0.48781946 | None | None | N |
| P/R | 0.1794 | likely_benign | 0.2177 | benign | 0.078 | Stabilizing | 0.317 | N | 0.348 | neutral | N | 0.508752093 | None | None | N |
| P/S | 0.0842 | likely_benign | 0.0858 | benign | -0.587 | Destabilizing | 0.027 | N | 0.323 | neutral | N | 0.474503446 | None | None | N |
| P/T | 0.074 | likely_benign | 0.0758 | benign | -0.59 | Destabilizing | 0.002 | N | 0.246 | neutral | N | 0.462160121 | None | None | N |
| P/V | 0.1417 | likely_benign | 0.1432 | benign | -0.283 | Destabilizing | 0.081 | N | 0.333 | neutral | None | None | None | None | N |
| P/W | 0.5455 | ambiguous | 0.5906 | pathogenic | -0.698 | Destabilizing | 0.935 | D | 0.494 | neutral | None | None | None | None | N |
| P/Y | 0.3527 | ambiguous | 0.3693 | ambiguous | -0.417 | Destabilizing | 0.555 | D | 0.368 | 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.