Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25950 | 78073;78074;78075 | chr2:178568284;178568283;178568282 | chr2:179433011;179433010;179433009 |
| N2AB | 24309 | 73150;73151;73152 | chr2:178568284;178568283;178568282 | chr2:179433011;179433010;179433009 |
| N2A | 23382 | 70369;70370;70371 | chr2:178568284;178568283;178568282 | chr2:179433011;179433010;179433009 |
| N2B | 16885 | 50878;50879;50880 | chr2:178568284;178568283;178568282 | chr2:179433011;179433010;179433009 |
| Novex-1 | 17010 | 51253;51254;51255 | chr2:178568284;178568283;178568282 | chr2:179433011;179433010;179433009 |
| Novex-2 | 17077 | 51454;51455;51456 | chr2:178568284;178568283;178568282 | chr2:179433011;179433010;179433009 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs376814602  |
-1.01 | 0.983 | N | 0.583 | 0.172 | None | gnomAD-2.1.1 | 1.74974E-04 | None | None | None | None | N | None | 0 | 5.66E-05 | None | 0 | 2.36601E-03 | None | 0 | None | 0 | 0 | 1.40528E-04 |
| L/F | rs376814602 |
-1.01 | 0.983 | N | 0.583 | 0.172 | None | gnomAD-3.1.2 | 1.97285E-04 | None | None | None | None | N | None | 0 | 1.18048E-03 | 0 | 0 | 2.12931E-03 | None | 0 | 0 | 0 | 0 | 4.78011E-04 |
| L/F | rs376814602 |
-1.01 | 0.983 | N | 0.583 | 0.172 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 3E-03 | 0 | None | None | None | 0 | None |
| L/F | rs376814602 |
-1.01 | 0.983 | N | 0.583 | 0.172 | None | gnomAD-4.0.0 | 6.44565E-05 | None | None | None | None | N | None | 0 | 3.335E-04 | None | 0 | 1.36173E-03 | None | 0 | 0 | 0 | 0 | 3.68212E-04 |
| L/I | None | None | 0.892 | N | 0.478 | 0.219 | 0.378674557249 | gnomAD-4.0.0 | 6.84317E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99575E-07 | 0 | 0 |
| L/V | rs376814602 |
-0.603 | 0.892 | N | 0.48 | 0.171 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| L/V | rs376814602 |
-0.603 | 0.892 | N | 0.48 | 0.171 | None | gnomAD-4.0.0 | 2.05295E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69873E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.7201 | likely_pathogenic | 0.6944 | pathogenic | -1.612 | Destabilizing | 0.128 | N | 0.409 | neutral | None | None | None | None | N |
| L/C | 0.6488 | likely_pathogenic | 0.6428 | pathogenic | -1.229 | Destabilizing | 0.154 | N | 0.473 | neutral | None | None | None | None | N |
| L/D | 0.9944 | likely_pathogenic | 0.9933 | pathogenic | -0.826 | Destabilizing | 0.987 | D | 0.797 | deleterious | None | None | None | None | N |
| L/E | 0.9571 | likely_pathogenic | 0.9487 | pathogenic | -0.695 | Destabilizing | 0.987 | D | 0.761 | deleterious | None | None | None | None | N |
| L/F | 0.2535 | likely_benign | 0.2502 | benign | -0.779 | Destabilizing | 0.983 | D | 0.583 | neutral | N | 0.449120291 | None | None | N |
| L/G | 0.9531 | likely_pathogenic | 0.9463 | pathogenic | -2.045 | Highly Destabilizing | 0.975 | D | 0.673 | neutral | None | None | None | None | N |
| L/H | 0.7912 | likely_pathogenic | 0.773 | pathogenic | -1.152 | Destabilizing | 0.999 | D | 0.784 | deleterious | N | 0.510208822 | None | None | N |
| L/I | 0.0964 | likely_benign | 0.0948 | benign | -0.442 | Destabilizing | 0.892 | D | 0.478 | neutral | N | 0.44100224 | None | None | N |
| L/K | 0.9227 | likely_pathogenic | 0.9086 | pathogenic | -1.174 | Destabilizing | 0.987 | D | 0.683 | prob.neutral | None | None | None | None | N |
| L/M | 0.1274 | likely_benign | 0.122 | benign | -0.545 | Destabilizing | 0.996 | D | 0.625 | neutral | None | None | None | None | N |
| L/N | 0.9354 | likely_pathogenic | 0.9212 | pathogenic | -1.335 | Destabilizing | 0.996 | D | 0.807 | deleterious | None | None | None | None | N |
| L/P | 0.9888 | likely_pathogenic | 0.9903 | pathogenic | -0.804 | Destabilizing | 0.983 | D | 0.799 | deleterious | N | 0.508314991 | None | None | N |
| L/Q | 0.7236 | likely_pathogenic | 0.6876 | pathogenic | -1.258 | Destabilizing | 0.996 | D | 0.749 | deleterious | None | None | None | None | N |
| L/R | 0.8636 | likely_pathogenic | 0.8478 | pathogenic | -0.845 | Destabilizing | 0.983 | D | 0.723 | prob.delet. | N | 0.507808012 | None | None | N |
| L/S | 0.8706 | likely_pathogenic | 0.8449 | pathogenic | -2.079 | Highly Destabilizing | 0.95 | D | 0.583 | neutral | None | None | None | None | N |
| L/T | 0.7001 | likely_pathogenic | 0.6487 | pathogenic | -1.8 | Destabilizing | 0.975 | D | 0.575 | neutral | None | None | None | None | N |
| L/V | 0.1167 | likely_benign | 0.1164 | benign | -0.804 | Destabilizing | 0.892 | D | 0.48 | neutral | N | 0.445269122 | None | None | N |
| L/W | 0.6772 | likely_pathogenic | 0.6663 | pathogenic | -0.942 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | None | None | None | None | N |
| L/Y | 0.7026 | likely_pathogenic | 0.693 | pathogenic | -0.67 | Destabilizing | 0.996 | D | 0.7 | prob.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.