Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19597 | 59014;59015;59016 | chr2:178593419;178593418;178593417 | chr2:179458146;179458145;179458144 |
| N2AB | 17956 | 54091;54092;54093 | chr2:178593419;178593418;178593417 | chr2:179458146;179458145;179458144 |
| N2A | 17029 | 51310;51311;51312 | chr2:178593419;178593418;178593417 | chr2:179458146;179458145;179458144 |
| N2B | 10532 | 31819;31820;31821 | chr2:178593419;178593418;178593417 | chr2:179458146;179458145;179458144 |
| Novex-1 | 10657 | 32194;32195;32196 | chr2:178593419;178593418;178593417 | chr2:179458146;179458145;179458144 |
| Novex-2 | 10724 | 32395;32396;32397 | chr2:178593419;178593418;178593417 | chr2:179458146;179458145;179458144 |
| 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/S | rs777654240  |
-2.524 | 0.997 | N | 0.781 | 0.382 | 0.570720304676 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| L/S | rs777654240 |
-2.524 | 0.997 | N | 0.781 | 0.382 | 0.570720304676 | gnomAD-4.0.0 | 1.59238E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.4334E-05 | 0 |
| L/V | rs201013593 |
-1.551 | 0.117 | N | 0.413 | 0.099 | 0.321672782286 | gnomAD-2.1.1 | 5.63E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.24327E-04 | 0 |
| L/V | rs201013593 |
-1.551 | 0.117 | N | 0.413 | 0.099 | 0.321672782286 | gnomAD-4.0.0 | 1.1635E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.52934E-05 | 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 | 0.2203 | likely_benign | 0.265 | benign | -2.238 | Highly Destabilizing | 0.966 | D | 0.615 | neutral | None | None | None | None | N |
| L/C | 0.4889 | ambiguous | 0.5442 | ambiguous | -1.615 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| L/D | 0.6682 | likely_pathogenic | 0.7655 | pathogenic | -2.315 | Highly Destabilizing | 0.999 | D | 0.868 | deleterious | None | None | None | None | N |
| L/E | 0.3693 | ambiguous | 0.4664 | ambiguous | -2.254 | Highly Destabilizing | 0.998 | D | 0.835 | deleterious | None | None | None | None | N |
| L/F | 0.1462 | likely_benign | 0.1662 | benign | -1.487 | Destabilizing | 0.997 | D | 0.705 | prob.neutral | N | 0.471800085 | None | None | N |
| L/G | 0.6081 | likely_pathogenic | 0.6959 | pathogenic | -2.613 | Highly Destabilizing | 0.998 | D | 0.825 | deleterious | None | None | None | None | N |
| L/H | 0.2685 | likely_benign | 0.3162 | benign | -1.76 | Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | N |
| L/I | 0.082 | likely_benign | 0.0867 | benign | -1.23 | Destabilizing | 0.955 | D | 0.579 | neutral | N | 0.486465171 | None | None | N |
| L/K | 0.3747 | ambiguous | 0.4447 | ambiguous | -1.619 | Destabilizing | 0.998 | D | 0.778 | deleterious | None | None | None | None | N |
| L/M | 0.1065 | likely_benign | 0.1167 | benign | -1.12 | Destabilizing | 0.998 | D | 0.74 | deleterious | None | None | None | None | N |
| L/N | 0.3493 | ambiguous | 0.4575 | ambiguous | -1.596 | Destabilizing | 0.999 | D | 0.867 | deleterious | None | None | None | None | N |
| L/P | 0.9212 | likely_pathogenic | 0.9385 | pathogenic | -1.541 | Destabilizing | 0.999 | D | 0.864 | deleterious | None | None | None | None | N |
| L/Q | 0.2104 | likely_benign | 0.249 | benign | -1.76 | Destabilizing | 0.999 | D | 0.851 | deleterious | None | None | None | None | N |
| L/R | 0.3196 | likely_benign | 0.3516 | ambiguous | -1.011 | Destabilizing | 0.998 | D | 0.845 | deleterious | None | None | None | None | N |
| L/S | 0.2404 | likely_benign | 0.3046 | benign | -2.217 | Highly Destabilizing | 0.997 | D | 0.781 | deleterious | N | 0.46272152 | None | None | N |
| L/T | 0.1334 | likely_benign | 0.1605 | benign | -2.045 | Highly Destabilizing | 0.995 | D | 0.711 | prob.delet. | None | None | None | None | N |
| L/V | 0.0785 | likely_benign | 0.0795 | benign | -1.541 | Destabilizing | 0.117 | N | 0.413 | neutral | N | 0.422587051 | None | None | N |
| L/W | 0.3061 | likely_benign | 0.3289 | benign | -1.62 | Destabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | N |
| L/Y | 0.334 | likely_benign | 0.3961 | ambiguous | -1.418 | Destabilizing | 0.999 | D | 0.814 | 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.