Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23671 | 71236;71237;71238 | chr2:178575121;178575120;178575119 | chr2:179439848;179439847;179439846 |
| N2AB | 22030 | 66313;66314;66315 | chr2:178575121;178575120;178575119 | chr2:179439848;179439847;179439846 |
| N2A | 21103 | 63532;63533;63534 | chr2:178575121;178575120;178575119 | chr2:179439848;179439847;179439846 |
| N2B | 14606 | 44041;44042;44043 | chr2:178575121;178575120;178575119 | chr2:179439848;179439847;179439846 |
| Novex-1 | 14731 | 44416;44417;44418 | chr2:178575121;178575120;178575119 | chr2:179439848;179439847;179439846 |
| Novex-2 | 14798 | 44617;44618;44619 | chr2:178575121;178575120;178575119 | chr2:179439848;179439847;179439846 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | None | None | 0.543 | N | 0.372 | 0.188 | 0.274366138417 | gnomAD-4.0.0 | 1.59315E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.027E-05 |
| D/E | None | None | 0.543 | N | 0.299 | 0.065 | 0.115124310173 | gnomAD-4.0.0 | 6.84562E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99724E-07 | 0 | 0 |
| D/H | None | None | 1.0 | N | 0.459 | 0.418 | 0.211220785272 | gnomAD-4.0.0 | 6.84586E-07 | None | None | None | None | I | None | 2.98972E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs774191400  |
0.386 | 0.998 | N | 0.515 | 0.257 | 0.139678290688 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs774191400 |
0.386 | 0.998 | N | 0.515 | 0.257 | 0.139678290688 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs774191400 |
0.386 | 0.998 | N | 0.515 | 0.257 | 0.139678290688 | gnomAD-4.0.0 | 1.86016E-06 | None | None | None | None | I | None | 2.67215E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47882E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1251 | likely_benign | 0.132 | benign | 0.069 | Stabilizing | 0.543 | D | 0.372 | neutral | N | 0.469303372 | None | None | I |
| D/C | 0.4624 | ambiguous | 0.4633 | ambiguous | -0.066 | Destabilizing | 1.0 | D | 0.58 | neutral | None | None | None | None | I |
| D/E | 0.0861 | likely_benign | 0.0922 | benign | -0.265 | Destabilizing | 0.543 | D | 0.299 | neutral | N | 0.498228455 | None | None | I |
| D/F | 0.4276 | ambiguous | 0.4361 | ambiguous | -0.032 | Destabilizing | 1.0 | D | 0.548 | neutral | None | None | None | None | I |
| D/G | 0.1089 | likely_benign | 0.1076 | benign | -0.043 | Destabilizing | 0.989 | D | 0.487 | neutral | N | 0.435574125 | None | None | I |
| D/H | 0.1939 | likely_benign | 0.1995 | benign | 0.536 | Stabilizing | 1.0 | D | 0.459 | neutral | N | 0.487914606 | None | None | I |
| D/I | 0.2166 | likely_benign | 0.2267 | benign | 0.294 | Stabilizing | 0.999 | D | 0.555 | neutral | None | None | None | None | I |
| D/K | 0.2027 | likely_benign | 0.2125 | benign | 0.496 | Stabilizing | 0.998 | D | 0.481 | neutral | None | None | None | None | I |
| D/L | 0.2441 | likely_benign | 0.2554 | benign | 0.294 | Stabilizing | 0.998 | D | 0.557 | neutral | None | None | None | None | I |
| D/M | 0.3668 | ambiguous | 0.3908 | ambiguous | 0.108 | Stabilizing | 1.0 | D | 0.549 | neutral | None | None | None | None | I |
| D/N | 0.0744 | likely_benign | 0.0753 | benign | 0.274 | Stabilizing | 0.998 | D | 0.515 | neutral | N | 0.459363422 | None | None | I |
| D/P | 0.3864 | ambiguous | 0.4113 | ambiguous | 0.238 | Stabilizing | 0.999 | D | 0.489 | neutral | None | None | None | None | I |
| D/Q | 0.1785 | likely_benign | 0.1916 | benign | 0.272 | Stabilizing | 0.998 | D | 0.522 | neutral | None | None | None | None | I |
| D/R | 0.2589 | likely_benign | 0.2617 | benign | 0.699 | Stabilizing | 0.998 | D | 0.476 | neutral | None | None | None | None | I |
| D/S | 0.0864 | likely_benign | 0.0895 | benign | 0.176 | Stabilizing | 0.983 | D | 0.483 | neutral | None | None | None | None | I |
| D/T | 0.1395 | likely_benign | 0.1506 | benign | 0.269 | Stabilizing | 0.998 | D | 0.475 | neutral | None | None | None | None | I |
| D/V | 0.1484 | likely_benign | 0.1541 | benign | 0.238 | Stabilizing | 0.997 | D | 0.543 | neutral | N | 0.481673635 | None | None | I |
| D/W | 0.7579 | likely_pathogenic | 0.7647 | pathogenic | None | Stabilizing | 1.0 | D | 0.605 | neutral | None | None | None | None | I |
| D/Y | 0.1884 | likely_benign | 0.1858 | benign | 0.194 | Stabilizing | 1.0 | D | 0.541 | neutral | N | 0.488168095 | 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.