Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29475 | 88648;88649;88650 | chr2:178555036;178555035;178555034 | chr2:179419763;179419762;179419761 |
| N2AB | 27834 | 83725;83726;83727 | chr2:178555036;178555035;178555034 | chr2:179419763;179419762;179419761 |
| N2A | 26907 | 80944;80945;80946 | chr2:178555036;178555035;178555034 | chr2:179419763;179419762;179419761 |
| N2B | 20410 | 61453;61454;61455 | chr2:178555036;178555035;178555034 | chr2:179419763;179419762;179419761 |
| Novex-1 | 20535 | 61828;61829;61830 | chr2:178555036;178555035;178555034 | chr2:179419763;179419762;179419761 |
| Novex-2 | 20602 | 62029;62030;62031 | chr2:178555036;178555035;178555034 | chr2:179419763;179419762;179419761 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/F | None | None | 0.005 | N | 0.199 | 0.059 | 0.185906805712 | gnomAD-4.0.0 | 1.36847E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79888E-06 | 0 | 0 |
| Y/H | rs1226553823  |
-2.071 | 0.028 | N | 0.337 | 0.175 | 0.263612267334 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| Y/H | rs1226553823 |
-2.071 | 0.028 | N | 0.337 | 0.175 | 0.263612267334 | gnomAD-4.0.0 | 9.57933E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.25923E-05 | 0 | 0 |
| Y/S | None | None | 0.891 | N | 0.594 | 0.271 | 0.561255953167 | gnomAD-4.0.0 | 6.84235E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15937E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.6444 | likely_pathogenic | 0.5392 | ambiguous | -2.992 | Highly Destabilizing | 0.915 | D | 0.568 | neutral | None | None | None | None | N |
| Y/C | 0.1381 | likely_benign | 0.1123 | benign | -1.419 | Destabilizing | 0.997 | D | 0.599 | neutral | N | 0.497404522 | None | None | N |
| Y/D | 0.5995 | likely_pathogenic | 0.4595 | ambiguous | -2.133 | Highly Destabilizing | 0.966 | D | 0.617 | neutral | N | 0.497231164 | None | None | N |
| Y/E | 0.7188 | likely_pathogenic | 0.6054 | pathogenic | -2.038 | Highly Destabilizing | 0.949 | D | 0.599 | neutral | None | None | None | None | N |
| Y/F | 0.0682 | likely_benign | 0.0654 | benign | -1.359 | Destabilizing | 0.005 | N | 0.199 | neutral | N | 0.410358754 | None | None | N |
| Y/G | 0.5763 | likely_pathogenic | 0.4816 | ambiguous | -3.32 | Highly Destabilizing | 0.915 | D | 0.597 | neutral | None | None | None | None | N |
| Y/H | 0.1597 | likely_benign | 0.1254 | benign | -1.618 | Destabilizing | 0.028 | N | 0.337 | neutral | N | 0.478202686 | None | None | N |
| Y/I | 0.4364 | ambiguous | 0.3443 | ambiguous | -1.955 | Destabilizing | 0.728 | D | 0.519 | neutral | None | None | None | None | N |
| Y/K | 0.4712 | ambiguous | 0.3862 | ambiguous | -1.627 | Destabilizing | 0.974 | D | 0.601 | neutral | None | None | None | None | N |
| Y/L | 0.378 | ambiguous | 0.3224 | benign | -1.955 | Destabilizing | 0.525 | D | 0.508 | neutral | None | None | None | None | N |
| Y/M | 0.4996 | ambiguous | 0.4348 | ambiguous | -1.536 | Destabilizing | 0.974 | D | 0.557 | neutral | None | None | None | None | N |
| Y/N | 0.2546 | likely_benign | 0.1932 | benign | -1.922 | Destabilizing | 0.934 | D | 0.598 | neutral | N | 0.497231164 | None | None | N |
| Y/P | 0.9929 | likely_pathogenic | 0.9871 | pathogenic | -2.303 | Highly Destabilizing | 0.991 | D | 0.634 | neutral | None | None | None | None | N |
| Y/Q | 0.4537 | ambiguous | 0.35 | ambiguous | -1.935 | Destabilizing | 0.974 | D | 0.565 | neutral | None | None | None | None | N |
| Y/R | 0.3498 | ambiguous | 0.2693 | benign | -1.018 | Destabilizing | 0.974 | D | 0.603 | neutral | None | None | None | None | N |
| Y/S | 0.3015 | likely_benign | 0.2279 | benign | -2.432 | Highly Destabilizing | 0.891 | D | 0.594 | neutral | N | 0.433065042 | None | None | N |
| Y/T | 0.4757 | ambiguous | 0.3992 | ambiguous | -2.243 | Highly Destabilizing | 0.974 | D | 0.599 | neutral | None | None | None | None | N |
| Y/V | 0.3818 | ambiguous | 0.3099 | benign | -2.303 | Highly Destabilizing | 0.842 | D | 0.471 | neutral | None | None | None | None | N |
| Y/W | 0.347 | ambiguous | 0.3082 | benign | -0.796 | Destabilizing | 0.991 | D | 0.523 | 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.