Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19767 | 59524;59525;59526 | chr2:178592820;178592819;178592818 | chr2:179457547;179457546;179457545 |
| N2AB | 18126 | 54601;54602;54603 | chr2:178592820;178592819;178592818 | chr2:179457547;179457546;179457545 |
| N2A | 17199 | 51820;51821;51822 | chr2:178592820;178592819;178592818 | chr2:179457547;179457546;179457545 |
| N2B | 10702 | 32329;32330;32331 | chr2:178592820;178592819;178592818 | chr2:179457547;179457546;179457545 |
| Novex-1 | 10827 | 32704;32705;32706 | chr2:178592820;178592819;178592818 | chr2:179457547;179457546;179457545 |
| Novex-2 | 10894 | 32905;32906;32907 | chr2:178592820;178592819;178592818 | chr2:179457547;179457546;179457545 |
| 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/E | rs2050519675  |
None | 0.003 | N | 0.155 | 0.066 | 0.0297737177859 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/E | rs2050519675 |
None | 0.003 | N | 0.155 | 0.066 | 0.0297737177859 | gnomAD-4.0.0 | 2.4792E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39085E-06 | 0 | 0 |
| D/N | rs1559606296 |
None | 0.018 | N | 0.273 | 0.117 | 0.159798565429 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65837E-04 |
| D/N | rs1559606296 |
None | 0.018 | N | 0.273 | 0.117 | 0.159798565429 | gnomAD-4.0.0 | 1.59191E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 2.41546E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1589 | likely_benign | 0.1511 | benign | -0.417 | Destabilizing | 0.565 | D | 0.578 | neutral | N | 0.467204619 | None | None | I |
| D/C | 0.6423 | likely_pathogenic | 0.5861 | pathogenic | -0.135 | Destabilizing | 0.996 | D | 0.748 | deleterious | None | None | None | None | I |
| D/E | 0.1065 | likely_benign | 0.1039 | benign | -0.393 | Destabilizing | 0.003 | N | 0.155 | neutral | N | 0.368021847 | None | None | I |
| D/F | 0.5492 | ambiguous | 0.4999 | ambiguous | -0.244 | Destabilizing | 0.996 | D | 0.701 | prob.neutral | None | None | None | None | I |
| D/G | 0.2513 | likely_benign | 0.2312 | benign | -0.644 | Destabilizing | 0.565 | D | 0.54 | neutral | N | 0.498642247 | None | None | I |
| D/H | 0.3348 | likely_benign | 0.2988 | benign | -0.127 | Destabilizing | 0.972 | D | 0.597 | neutral | N | 0.502549344 | None | None | I |
| D/I | 0.2752 | likely_benign | 0.252 | benign | 0.143 | Stabilizing | 0.961 | D | 0.693 | prob.neutral | None | None | None | None | I |
| D/K | 0.3274 | likely_benign | 0.2984 | benign | -0.014 | Destabilizing | 0.633 | D | 0.573 | neutral | None | None | None | None | I |
| D/L | 0.2783 | likely_benign | 0.2646 | benign | 0.143 | Stabilizing | 0.923 | D | 0.651 | neutral | None | None | None | None | I |
| D/M | 0.4909 | ambiguous | 0.4637 | ambiguous | 0.31 | Stabilizing | 0.996 | D | 0.707 | prob.neutral | None | None | None | None | I |
| D/N | 0.1314 | likely_benign | 0.1182 | benign | -0.29 | Destabilizing | 0.018 | N | 0.273 | neutral | N | 0.502722702 | None | None | I |
| D/P | 0.4296 | ambiguous | 0.4347 | ambiguous | -0.022 | Destabilizing | 0.961 | D | 0.592 | neutral | None | None | None | None | I |
| D/Q | 0.2815 | likely_benign | 0.2694 | benign | -0.241 | Destabilizing | 0.858 | D | 0.505 | neutral | None | None | None | None | I |
| D/R | 0.4153 | ambiguous | 0.3757 | ambiguous | 0.242 | Stabilizing | 0.923 | D | 0.637 | neutral | None | None | None | None | I |
| D/S | 0.1455 | likely_benign | 0.133 | benign | -0.44 | Destabilizing | 0.633 | D | 0.489 | neutral | None | None | None | None | I |
| D/T | 0.2398 | likely_benign | 0.2235 | benign | -0.266 | Destabilizing | 0.923 | D | 0.542 | neutral | None | None | None | None | I |
| D/V | 0.1686 | likely_benign | 0.1567 | benign | -0.022 | Destabilizing | 0.901 | D | 0.647 | neutral | N | 0.47291987 | None | None | I |
| D/W | 0.8657 | likely_pathogenic | 0.852 | pathogenic | -0.083 | Destabilizing | 0.996 | D | 0.72 | prob.delet. | None | None | None | None | I |
| D/Y | 0.2627 | likely_benign | 0.2342 | benign | -0.014 | Destabilizing | 0.983 | D | 0.701 | prob.neutral | N | 0.49054945 | 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.