Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25566 | 76921;76922;76923 | chr2:178569436;178569435;178569434 | chr2:179434163;179434162;179434161 |
| N2AB | 23925 | 71998;71999;72000 | chr2:178569436;178569435;178569434 | chr2:179434163;179434162;179434161 |
| N2A | 22998 | 69217;69218;69219 | chr2:178569436;178569435;178569434 | chr2:179434163;179434162;179434161 |
| N2B | 16501 | 49726;49727;49728 | chr2:178569436;178569435;178569434 | chr2:179434163;179434162;179434161 |
| Novex-1 | 16626 | 50101;50102;50103 | chr2:178569436;178569435;178569434 | chr2:179434163;179434162;179434161 |
| Novex-2 | 16693 | 50302;50303;50304 | chr2:178569436;178569435;178569434 | chr2:179434163;179434162;179434161 |
| 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/P | rs1323717498  |
-1.447 | 1.0 | D | 0.847 | 0.873 | 0.90521616659 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.6E-05 | None | 0 | None | 0 | 0 | 0 |
| L/P | rs1323717498 |
-1.447 | 1.0 | D | 0.847 | 0.873 | 0.90521616659 | gnomAD-4.0.0 | 1.36888E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52512E-05 | None | 0 | 0 | 8.99661E-07 | 0 | 0 |
| L/V | rs1332447067 |
-1.081 | 0.999 | D | 0.665 | 0.72 | 0.735321164879 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 9.98E-05 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/V | rs1332447067 |
-1.081 | 0.999 | D | 0.665 | 0.72 | 0.735321164879 | gnomAD-4.0.0 | 1.36889E-06 | None | None | None | None | N | None | 0 | 0 | None | 7.6599E-05 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9252 | likely_pathogenic | 0.9357 | pathogenic | -2.483 | Highly Destabilizing | 0.999 | D | 0.704 | prob.neutral | None | None | None | None | N |
| L/C | 0.9005 | likely_pathogenic | 0.9189 | pathogenic | -1.845 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| L/D | 0.9997 | likely_pathogenic | 0.9997 | pathogenic | -3.113 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| L/E | 0.9978 | likely_pathogenic | 0.9977 | pathogenic | -2.786 | Highly Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| L/F | 0.4283 | ambiguous | 0.4753 | ambiguous | -1.538 | Destabilizing | 1.0 | D | 0.767 | deleterious | N | 0.504417192 | None | None | N |
| L/G | 0.9945 | likely_pathogenic | 0.9953 | pathogenic | -3.102 | Highly Destabilizing | 1.0 | D | 0.834 | deleterious | None | None | None | None | N |
| L/H | 0.99 | likely_pathogenic | 0.9909 | pathogenic | -2.857 | Highly Destabilizing | 1.0 | D | 0.809 | deleterious | D | 0.570139169 | None | None | N |
| L/I | 0.191 | likely_benign | 0.1878 | benign | -0.634 | Destabilizing | 0.999 | D | 0.66 | neutral | N | 0.516899133 | None | None | N |
| L/K | 0.9952 | likely_pathogenic | 0.995 | pathogenic | -2.049 | Highly Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| L/M | 0.2267 | likely_benign | 0.2781 | benign | -0.751 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| L/N | 0.9981 | likely_pathogenic | 0.9982 | pathogenic | -2.754 | Highly Destabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | None | N |
| L/P | 0.9985 | likely_pathogenic | 0.9985 | pathogenic | -1.238 | Destabilizing | 1.0 | D | 0.847 | deleterious | D | 0.570139169 | None | None | N |
| L/Q | 0.9892 | likely_pathogenic | 0.9904 | pathogenic | -2.369 | Highly Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| L/R | 0.9898 | likely_pathogenic | 0.9896 | pathogenic | -2.18 | Highly Destabilizing | 1.0 | D | 0.839 | deleterious | D | 0.570139169 | None | None | N |
| L/S | 0.9938 | likely_pathogenic | 0.9949 | pathogenic | -3.359 | Highly Destabilizing | 1.0 | D | 0.838 | deleterious | None | None | None | None | N |
| L/T | 0.9755 | likely_pathogenic | 0.9776 | pathogenic | -2.852 | Highly Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| L/V | 0.2116 | likely_benign | 0.2206 | benign | -1.238 | Destabilizing | 0.999 | D | 0.665 | neutral | D | 0.534131242 | None | None | N |
| L/W | 0.9513 | likely_pathogenic | 0.9587 | pathogenic | -1.942 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| L/Y | 0.9457 | likely_pathogenic | 0.9546 | pathogenic | -1.661 | Destabilizing | 1.0 | D | 0.789 | deleterious | 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.