Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27089 | 81490;81491;81492 | chr2:178564867;178564866;178564865 | chr2:179429594;179429593;179429592 |
| N2AB | 25448 | 76567;76568;76569 | chr2:178564867;178564866;178564865 | chr2:179429594;179429593;179429592 |
| N2A | 24521 | 73786;73787;73788 | chr2:178564867;178564866;178564865 | chr2:179429594;179429593;179429592 |
| N2B | 18024 | 54295;54296;54297 | chr2:178564867;178564866;178564865 | chr2:179429594;179429593;179429592 |
| Novex-1 | 18149 | 54670;54671;54672 | chr2:178564867;178564866;178564865 | chr2:179429594;179429593;179429592 |
| Novex-2 | 18216 | 54871;54872;54873 | chr2:178564867;178564866;178564865 | chr2:179429594;179429593;179429592 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs1213075962  |
-0.032 | 0.985 | N | 0.635 | 0.382 | 0.380223377699 | gnomAD-2.1.1 | 8.09E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.62E-05 | None | 0 | None | 4.66E-05 | 0 | 0 |
| M/I | rs1213075962 |
-0.032 | 0.985 | N | 0.635 | 0.382 | 0.380223377699 | gnomAD-4.0.0 | 1.59346E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78071E-05 | None | 0 | 0 | 0 | 0 | 0 |
| M/K | None | None | 0.994 | N | 0.777 | 0.585 | 0.716981834949 | gnomAD-4.0.0 | 3.18655E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88437E-05 | 0 | 0 | 0 | 3.03141E-05 |
| M/R | None | None | 0.998 | N | 0.817 | 0.566 | 0.717962116301 | gnomAD-4.0.0 | 1.59328E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86002E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.7814 | likely_pathogenic | 0.772 | pathogenic | -1.823 | Destabilizing | 0.989 | D | 0.695 | prob.neutral | None | None | None | None | N |
| M/C | 0.8281 | likely_pathogenic | 0.8265 | pathogenic | -2.251 | Highly Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| M/D | 0.9983 | likely_pathogenic | 0.998 | pathogenic | -1.986 | Destabilizing | 0.999 | D | 0.821 | deleterious | None | None | None | None | N |
| M/E | 0.9869 | likely_pathogenic | 0.9841 | pathogenic | -1.724 | Destabilizing | 0.999 | D | 0.781 | deleterious | None | None | None | None | N |
| M/F | 0.771 | likely_pathogenic | 0.7277 | pathogenic | -0.426 | Destabilizing | 0.999 | D | 0.71 | prob.delet. | None | None | None | None | N |
| M/G | 0.9572 | likely_pathogenic | 0.9541 | pathogenic | -2.307 | Highly Destabilizing | 0.995 | D | 0.762 | deleterious | None | None | None | None | N |
| M/H | 0.9892 | likely_pathogenic | 0.9869 | pathogenic | -2.179 | Highly Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| M/I | 0.5758 | likely_pathogenic | 0.5452 | ambiguous | -0.426 | Destabilizing | 0.985 | D | 0.635 | neutral | N | 0.434129409 | None | None | N |
| M/K | 0.9641 | likely_pathogenic | 0.959 | pathogenic | -1.076 | Destabilizing | 0.994 | D | 0.777 | deleterious | N | 0.511629446 | None | None | N |
| M/L | 0.3295 | likely_benign | 0.2932 | benign | -0.426 | Destabilizing | 0.927 | D | 0.409 | neutral | N | 0.48141635 | None | None | N |
| M/N | 0.9807 | likely_pathogenic | 0.9783 | pathogenic | -1.57 | Destabilizing | 0.999 | D | 0.798 | deleterious | None | None | None | None | N |
| M/P | 0.9979 | likely_pathogenic | 0.9977 | pathogenic | -0.875 | Destabilizing | 0.999 | D | 0.799 | deleterious | None | None | None | None | N |
| M/Q | 0.8945 | likely_pathogenic | 0.8836 | pathogenic | -1.166 | Destabilizing | 0.999 | D | 0.725 | prob.delet. | None | None | None | None | N |
| M/R | 0.9673 | likely_pathogenic | 0.9618 | pathogenic | -1.45 | Destabilizing | 0.998 | D | 0.817 | deleterious | N | 0.511629446 | None | None | N |
| M/S | 0.9227 | likely_pathogenic | 0.9143 | pathogenic | -2.041 | Highly Destabilizing | 0.995 | D | 0.756 | deleterious | None | None | None | None | N |
| M/T | 0.9119 | likely_pathogenic | 0.8887 | pathogenic | -1.644 | Destabilizing | 0.994 | D | 0.773 | deleterious | N | 0.493182796 | None | None | N |
| M/V | 0.2411 | likely_benign | 0.2181 | benign | -0.875 | Destabilizing | 0.985 | D | 0.507 | neutral | N | 0.441266025 | None | None | N |
| M/W | 0.992 | likely_pathogenic | 0.9881 | pathogenic | -0.806 | Destabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | N |
| M/Y | 0.967 | likely_pathogenic | 0.9599 | pathogenic | -0.719 | Destabilizing | 0.999 | D | 0.821 | 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.