Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28544 | 85855;85856;85857 | chr2:178560502;178560501;178560500 | chr2:179425229;179425228;179425227 |
| N2AB | 26903 | 80932;80933;80934 | chr2:178560502;178560501;178560500 | chr2:179425229;179425228;179425227 |
| N2A | 25976 | 78151;78152;78153 | chr2:178560502;178560501;178560500 | chr2:179425229;179425228;179425227 |
| N2B | 19479 | 58660;58661;58662 | chr2:178560502;178560501;178560500 | chr2:179425229;179425228;179425227 |
| Novex-1 | 19604 | 59035;59036;59037 | chr2:178560502;178560501;178560500 | chr2:179425229;179425228;179425227 |
| Novex-2 | 19671 | 59236;59237;59238 | chr2:178560502;178560501;178560500 | chr2:179425229;179425228;179425227 |
| 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/V | rs775485220  |
-0.492 | 0.841 | N | 0.593 | 0.195 | 0.495573750707 | gnomAD-2.1.1 | 1.08E-05 | None | None | None | None | N | None | 1.24111E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/V | rs775485220 |
-0.492 | 0.841 | N | 0.593 | 0.195 | 0.495573750707 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs775485220 |
-0.492 | 0.841 | N | 0.593 | 0.195 | 0.495573750707 | gnomAD-4.0.0 | 3.848E-06 | None | None | None | None | N | None | 5.08147E-05 | 0 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5785 | likely_pathogenic | 0.5919 | pathogenic | -1.638 | Destabilizing | 0.999 | D | 0.751 | deleterious | None | None | None | None | N |
| A/D | 0.9665 | likely_pathogenic | 0.9643 | pathogenic | -2.666 | Highly Destabilizing | 0.98 | D | 0.804 | deleterious | None | None | None | None | N |
| A/E | 0.9335 | likely_pathogenic | 0.9359 | pathogenic | -2.502 | Highly Destabilizing | 0.974 | D | 0.727 | deleterious | D | 0.538280347 | None | None | N |
| A/F | 0.7138 | likely_pathogenic | 0.7196 | pathogenic | -0.861 | Destabilizing | 0.99 | D | 0.8 | deleterious | None | None | None | None | N |
| A/G | 0.4054 | ambiguous | 0.4119 | ambiguous | -1.72 | Destabilizing | 0.914 | D | 0.577 | neutral | N | 0.52144354 | None | None | N |
| A/H | 0.9668 | likely_pathogenic | 0.9652 | pathogenic | -1.939 | Destabilizing | 0.999 | D | 0.791 | deleterious | None | None | None | None | N |
| A/I | 0.2835 | likely_benign | 0.3032 | benign | -0.169 | Destabilizing | 0.98 | D | 0.787 | deleterious | None | None | None | None | N |
| A/K | 0.976 | likely_pathogenic | 0.9764 | pathogenic | -1.353 | Destabilizing | 0.98 | D | 0.743 | deleterious | None | None | None | None | N |
| A/L | 0.3184 | likely_benign | 0.3289 | benign | -0.169 | Destabilizing | 0.875 | D | 0.711 | prob.delet. | None | None | None | None | N |
| A/M | 0.3376 | likely_benign | 0.3487 | ambiguous | -0.537 | Destabilizing | 0.999 | D | 0.81 | deleterious | None | None | None | None | N |
| A/N | 0.8637 | likely_pathogenic | 0.866 | pathogenic | -1.658 | Destabilizing | 0.98 | D | 0.799 | deleterious | None | None | None | None | N |
| A/P | 0.5706 | likely_pathogenic | 0.5867 | pathogenic | -0.504 | Destabilizing | 0.987 | D | 0.804 | deleterious | N | 0.505314294 | None | None | N |
| A/Q | 0.909 | likely_pathogenic | 0.9111 | pathogenic | -1.534 | Destabilizing | 0.99 | D | 0.805 | deleterious | None | None | None | None | N |
| A/R | 0.9481 | likely_pathogenic | 0.9472 | pathogenic | -1.346 | Destabilizing | 0.98 | D | 0.803 | deleterious | None | None | None | None | N |
| A/S | 0.2657 | likely_benign | 0.2742 | benign | -2.048 | Highly Destabilizing | 0.841 | D | 0.594 | neutral | N | 0.515910131 | None | None | N |
| A/T | 0.3051 | likely_benign | 0.3363 | benign | -1.77 | Destabilizing | 0.071 | N | 0.342 | neutral | D | 0.52399177 | None | None | N |
| A/V | 0.1454 | likely_benign | 0.1672 | benign | -0.504 | Destabilizing | 0.841 | D | 0.593 | neutral | N | 0.500501622 | None | None | N |
| A/W | 0.9791 | likely_pathogenic | 0.9797 | pathogenic | -1.532 | Destabilizing | 0.999 | D | 0.797 | deleterious | None | None | None | None | N |
| A/Y | 0.8967 | likely_pathogenic | 0.8926 | pathogenic | -1.065 | Destabilizing | 0.999 | D | 0.801 | 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.