Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20002 | 60229;60230;60231 | chr2:178591815;178591814;178591813 | chr2:179456542;179456541;179456540 |
| N2AB | 18361 | 55306;55307;55308 | chr2:178591815;178591814;178591813 | chr2:179456542;179456541;179456540 |
| N2A | 17434 | 52525;52526;52527 | chr2:178591815;178591814;178591813 | chr2:179456542;179456541;179456540 |
| N2B | 10937 | 33034;33035;33036 | chr2:178591815;178591814;178591813 | chr2:179456542;179456541;179456540 |
| Novex-1 | 11062 | 33409;33410;33411 | chr2:178591815;178591814;178591813 | chr2:179456542;179456541;179456540 |
| Novex-2 | 11129 | 33610;33611;33612 | chr2:178591815;178591814;178591813 | chr2:179456542;179456541;179456540 |
| 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/G | rs199512049  |
-0.211 | 1.0 | N | 0.672 | 0.493 | None | gnomAD-2.1.1 | 5.5111E-04 | None | None | None | None | N | None | 0 | 0 | None | 1.28801E-02 | 0 | None | 0 | None | 0 | 1.2538E-04 | 7.03829E-04 |
| D/G | rs199512049 |
-0.211 | 1.0 | N | 0.672 | 0.493 | None | gnomAD-3.1.2 | 3.09052E-04 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 1.0951E-02 | 0 | None | 0 | 0 | 1.02953E-04 | 0 | 4.77555E-04 |
| D/G | rs199512049 |
-0.211 | 1.0 | N | 0.672 | 0.493 | None | gnomAD-4.0.0 | 3.13045E-04 | None | None | None | None | N | None | 2.67044E-05 | 3.33756E-05 | None | 1.26386E-02 | 0 | None | 0 | 0 | 6.01907E-05 | 0 | 8.96861E-04 |
| D/H | None | None | 1.0 | N | 0.635 | 0.442 | 0.449474494731 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 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 | 0.2683 | likely_benign | 0.2947 | benign | -0.049 | Destabilizing | 1.0 | D | 0.765 | deleterious | N | 0.469628849 | None | None | N |
| D/C | 0.7974 | likely_pathogenic | 0.8555 | pathogenic | -0.063 | Destabilizing | 1.0 | D | 0.708 | prob.delet. | None | None | None | None | N |
| D/E | 0.2148 | likely_benign | 0.242 | benign | -0.249 | Destabilizing | 1.0 | D | 0.447 | neutral | N | 0.456179549 | None | None | N |
| D/F | 0.7058 | likely_pathogenic | 0.7548 | pathogenic | -0.11 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| D/G | 0.3672 | ambiguous | 0.4024 | ambiguous | -0.193 | Destabilizing | 1.0 | D | 0.672 | neutral | N | 0.447658854 | None | None | N |
| D/H | 0.472 | ambiguous | 0.5344 | ambiguous | 0.302 | Stabilizing | 1.0 | D | 0.635 | neutral | N | 0.469571586 | None | None | N |
| D/I | 0.3873 | ambiguous | 0.4541 | ambiguous | 0.27 | Stabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| D/K | 0.5496 | ambiguous | 0.6031 | pathogenic | 0.348 | Stabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| D/L | 0.3934 | ambiguous | 0.4257 | ambiguous | 0.27 | Stabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| D/M | 0.6811 | likely_pathogenic | 0.7245 | pathogenic | 0.148 | Stabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| D/N | 0.1787 | likely_benign | 0.1999 | benign | 0.188 | Stabilizing | 1.0 | D | 0.625 | neutral | N | 0.496604807 | None | None | N |
| D/P | 0.7094 | likely_pathogenic | 0.7556 | pathogenic | 0.184 | Stabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| D/Q | 0.4788 | ambiguous | 0.5365 | ambiguous | 0.186 | Stabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | N |
| D/R | 0.5908 | likely_pathogenic | 0.6527 | pathogenic | 0.566 | Stabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| D/S | 0.2163 | likely_benign | 0.2445 | benign | 0.063 | Stabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| D/T | 0.3768 | ambiguous | 0.4256 | ambiguous | 0.171 | Stabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| D/V | 0.2555 | likely_benign | 0.2992 | benign | 0.184 | Stabilizing | 1.0 | D | 0.753 | deleterious | N | 0.462204231 | None | None | N |
| D/W | 0.908 | likely_pathogenic | 0.936 | pathogenic | -0.052 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | N |
| D/Y | 0.3484 | ambiguous | 0.4068 | ambiguous | 0.115 | Stabilizing | 1.0 | D | 0.693 | prob.neutral | N | 0.48143487 | 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.