Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35301 | 106126;106127;106128 | chr2:178530714;178530713;178530712 | chr2:179395441;179395440;179395439 |
| N2AB | 33660 | 101203;101204;101205 | chr2:178530714;178530713;178530712 | chr2:179395441;179395440;179395439 |
| N2A | 32733 | 98422;98423;98424 | chr2:178530714;178530713;178530712 | chr2:179395441;179395440;179395439 |
| N2B | 26236 | 78931;78932;78933 | chr2:178530714;178530713;178530712 | chr2:179395441;179395440;179395439 |
| Novex-1 | 26361 | 79306;79307;79308 | chr2:178530714;178530713;178530712 | chr2:179395441;179395440;179395439 |
| Novex-2 | 26428 | 79507;79508;79509 | chr2:178530714;178530713;178530712 | chr2:179395441;179395440;179395439 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/E | rs1354185370  |
None | 0.761 | N | 0.673 | 0.26 | 0.377274123778 | gnomAD-4.0.0 | 6.84151E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65645E-05 |
| A/V | rs1354185370 |
0.467 | 0.001 | N | 0.163 | 0.093 | 0.1749357433 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| A/V | rs1354185370 |
0.467 | 0.001 | N | 0.163 | 0.093 | 0.1749357433 | gnomAD-4.0.0 | 1.3683E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31868E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6117 | likely_pathogenic | 0.6197 | pathogenic | -1.338 | Destabilizing | 0.978 | D | 0.656 | neutral | None | None | None | None | N |
| A/D | 0.9576 | likely_pathogenic | 0.9396 | pathogenic | -1.536 | Destabilizing | 0.937 | D | 0.731 | prob.delet. | None | None | None | None | N |
| A/E | 0.902 | likely_pathogenic | 0.8618 | pathogenic | -1.436 | Destabilizing | 0.761 | D | 0.673 | neutral | N | 0.489371593 | None | None | N |
| A/F | 0.694 | likely_pathogenic | 0.6594 | pathogenic | -0.904 | Destabilizing | 0.879 | D | 0.731 | prob.delet. | None | None | None | None | N |
| A/G | 0.2804 | likely_benign | 0.2977 | benign | -1.52 | Destabilizing | 0.002 | N | 0.225 | neutral | N | 0.456935292 | None | None | N |
| A/H | 0.9489 | likely_pathogenic | 0.9356 | pathogenic | -1.758 | Destabilizing | 0.994 | D | 0.672 | neutral | None | None | None | None | N |
| A/I | 0.3082 | likely_benign | 0.3089 | benign | -0.091 | Destabilizing | 0.027 | N | 0.399 | neutral | None | None | None | None | N |
| A/K | 0.955 | likely_pathogenic | 0.9379 | pathogenic | -1.323 | Destabilizing | 0.808 | D | 0.681 | prob.neutral | None | None | None | None | N |
| A/L | 0.2861 | likely_benign | 0.2813 | benign | -0.091 | Destabilizing | 0.158 | N | 0.501 | neutral | None | None | None | None | N |
| A/M | 0.4316 | ambiguous | 0.4208 | ambiguous | -0.272 | Destabilizing | 0.937 | D | 0.709 | prob.delet. | None | None | None | None | N |
| A/N | 0.8921 | likely_pathogenic | 0.8743 | pathogenic | -1.332 | Destabilizing | 0.937 | D | 0.73 | prob.delet. | None | None | None | None | N |
| A/P | 0.9363 | likely_pathogenic | 0.914 | pathogenic | -0.386 | Destabilizing | 0.971 | D | 0.743 | deleterious | N | 0.477761798 | None | None | N |
| A/Q | 0.8686 | likely_pathogenic | 0.8443 | pathogenic | -1.282 | Destabilizing | 0.978 | D | 0.741 | deleterious | None | None | None | None | N |
| A/R | 0.9157 | likely_pathogenic | 0.888 | pathogenic | -1.238 | Destabilizing | 0.937 | D | 0.736 | prob.delet. | None | None | None | None | N |
| A/S | 0.2269 | likely_benign | 0.2317 | benign | -1.841 | Destabilizing | 0.611 | D | 0.563 | neutral | N | 0.459404054 | None | None | N |
| A/T | 0.1661 | likely_benign | 0.162 | benign | -1.609 | Destabilizing | 0.611 | D | 0.573 | neutral | N | 0.493411707 | None | None | N |
| A/V | 0.1298 | likely_benign | 0.1282 | benign | -0.386 | Destabilizing | 0.001 | N | 0.163 | neutral | N | 0.422890042 | None | None | N |
| A/W | 0.9687 | likely_pathogenic | 0.9595 | pathogenic | -1.424 | Destabilizing | 0.994 | D | 0.701 | prob.neutral | None | None | None | None | N |
| A/Y | 0.9 | likely_pathogenic | 0.8783 | pathogenic | -0.936 | Destabilizing | 0.937 | D | 0.73 | prob.delet. | 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.