Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2858 | 8797;8798;8799 | chr2:178770129;178770128;178770127 | chr2:179634856;179634855;179634854 |
| N2AB | 2858 | 8797;8798;8799 | chr2:178770129;178770128;178770127 | chr2:179634856;179634855;179634854 |
| N2A | 2858 | 8797;8798;8799 | chr2:178770129;178770128;178770127 | chr2:179634856;179634855;179634854 |
| N2B | 2812 | 8659;8660;8661 | chr2:178770129;178770128;178770127 | chr2:179634856;179634855;179634854 |
| Novex-1 | 2812 | 8659;8660;8661 | chr2:178770129;178770128;178770127 | chr2:179634856;179634855;179634854 |
| Novex-2 | 2812 | 8659;8660;8661 | chr2:178770129;178770128;178770127 | chr2:179634856;179634855;179634854 |
| Novex-3 | 2858 | 8797;8798;8799 | chr2:178770129;178770128;178770127 | chr2:179634856;179634855;179634854 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs370094744  |
-0.063 | 0.549 | N | 0.383 | 0.299 | None | gnomAD-2.1.1 | 1.42E-05 | None | None | None | None | N | None | 1.20163E-04 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| P/L | rs370094744 |
-0.063 | 0.549 | N | 0.383 | 0.299 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/L | rs370094744 |
-0.063 | 0.549 | N | 0.383 | 0.299 | None | gnomAD-4.0.0 | 7.435E-06 | None | None | None | None | N | None | 8.00961E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47448E-07 | 5.48992E-05 | 0 |
| P/R | rs370094744 |
None | 0.379 | N | 0.33 | 0.261 | 0.267755039894 | gnomAD-4.0.0 | 6.84067E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65574E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.075 | likely_benign | 0.0782 | benign | -0.423 | Destabilizing | 0.201 | N | 0.25 | neutral | N | 0.445231749 | None | None | N |
| P/C | 0.4557 | ambiguous | 0.5005 | ambiguous | -0.577 | Destabilizing | 0.992 | D | 0.342 | neutral | None | None | None | None | N |
| P/D | 0.4409 | ambiguous | 0.4354 | ambiguous | -0.197 | Destabilizing | 0.447 | N | 0.253 | neutral | None | None | None | None | N |
| P/E | 0.2966 | likely_benign | 0.2835 | benign | -0.32 | Destabilizing | 0.021 | N | 0.187 | neutral | None | None | None | None | N |
| P/F | 0.4473 | ambiguous | 0.4528 | ambiguous | -0.736 | Destabilizing | 0.92 | D | 0.339 | neutral | None | None | None | None | N |
| P/G | 0.2654 | likely_benign | 0.2933 | benign | -0.543 | Destabilizing | 0.002 | N | 0.189 | neutral | None | None | None | None | N |
| P/H | 0.1834 | likely_benign | 0.1817 | benign | -0.178 | Destabilizing | 0.896 | D | 0.299 | neutral | N | 0.436207575 | None | None | N |
| P/I | 0.2492 | likely_benign | 0.2608 | benign | -0.264 | Destabilizing | 0.92 | D | 0.368 | neutral | None | None | None | None | N |
| P/K | 0.2785 | likely_benign | 0.2722 | benign | -0.316 | Destabilizing | 0.021 | N | 0.179 | neutral | None | None | None | None | N |
| P/L | 0.1105 | likely_benign | 0.1102 | benign | -0.264 | Destabilizing | 0.549 | D | 0.383 | neutral | N | 0.444516045 | None | None | N |
| P/M | 0.2835 | likely_benign | 0.3164 | benign | -0.256 | Destabilizing | 0.992 | D | 0.301 | neutral | None | None | None | None | N |
| P/N | 0.2934 | likely_benign | 0.3085 | benign | -0.046 | Destabilizing | 0.447 | N | 0.337 | neutral | None | None | None | None | N |
| P/Q | 0.1512 | likely_benign | 0.1536 | benign | -0.309 | Destabilizing | 0.617 | D | 0.324 | neutral | None | None | None | None | N |
| P/R | 0.1899 | likely_benign | 0.1818 | benign | 0.182 | Stabilizing | 0.379 | N | 0.33 | neutral | N | 0.438691348 | None | None | N |
| P/S | 0.1057 | likely_benign | 0.11 | benign | -0.412 | Destabilizing | 0.007 | N | 0.154 | neutral | N | 0.449077319 | None | None | N |
| P/T | 0.107 | likely_benign | 0.1109 | benign | -0.435 | Destabilizing | 0.379 | N | 0.246 | neutral | N | 0.452209127 | None | None | N |
| P/V | 0.1653 | likely_benign | 0.1771 | benign | -0.282 | Destabilizing | 0.617 | D | 0.352 | neutral | None | None | None | None | N |
| P/W | 0.6571 | likely_pathogenic | 0.6811 | pathogenic | -0.809 | Destabilizing | 0.992 | D | 0.409 | neutral | None | None | None | None | N |
| P/Y | 0.411 | ambiguous | 0.4142 | ambiguous | -0.489 | Destabilizing | 0.972 | D | 0.341 | 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.