Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32214 | 96865;96866;96867 | chr2:178543333;178543332;178543331 | chr2:179408060;179408059;179408058 |
| N2AB | 30573 | 91942;91943;91944 | chr2:178543333;178543332;178543331 | chr2:179408060;179408059;179408058 |
| N2A | 29646 | 89161;89162;89163 | chr2:178543333;178543332;178543331 | chr2:179408060;179408059;179408058 |
| N2B | 23149 | 69670;69671;69672 | chr2:178543333;178543332;178543331 | chr2:179408060;179408059;179408058 |
| Novex-1 | 23274 | 70045;70046;70047 | chr2:178543333;178543332;178543331 | chr2:179408060;179408059;179408058 |
| Novex-2 | 23341 | 70246;70247;70248 | chr2:178543333;178543332;178543331 | chr2:179408060;179408059;179408058 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/G | None | None | 0.993 | D | 0.67 | 0.465 | 0.792547075834 | gnomAD-4.0.0 | 1.59113E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85804E-06 | 0 | 0 |
| V/I | rs1486085185  |
-0.786 | 0.449 | N | 0.495 | 0.123 | 0.37762505005 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| V/I | rs1486085185 |
-0.786 | 0.449 | N | 0.495 | 0.123 | 0.37762505005 | gnomAD-4.0.0 | 6.84185E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.51978E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3135 | likely_benign | 0.3111 | benign | -1.686 | Destabilizing | 0.724 | D | 0.495 | neutral | N | 0.471296787 | None | None | N |
| V/C | 0.7909 | likely_pathogenic | 0.7949 | pathogenic | -1.874 | Destabilizing | 0.999 | D | 0.618 | neutral | None | None | None | None | N |
| V/D | 0.8168 | likely_pathogenic | 0.8242 | pathogenic | -2.385 | Highly Destabilizing | 0.991 | D | 0.727 | prob.delet. | N | 0.507772013 | None | None | N |
| V/E | 0.6349 | likely_pathogenic | 0.6507 | pathogenic | -2.337 | Highly Destabilizing | 0.959 | D | 0.619 | neutral | None | None | None | None | N |
| V/F | 0.4293 | ambiguous | 0.4442 | ambiguous | -1.403 | Destabilizing | 0.994 | D | 0.659 | neutral | N | 0.495708146 | None | None | N |
| V/G | 0.4545 | ambiguous | 0.4644 | ambiguous | -2.023 | Highly Destabilizing | 0.993 | D | 0.67 | neutral | D | 0.531663166 | None | None | N |
| V/H | 0.8312 | likely_pathogenic | 0.8345 | pathogenic | -1.561 | Destabilizing | 0.999 | D | 0.712 | prob.delet. | None | None | None | None | N |
| V/I | 0.089 | likely_benign | 0.0853 | benign | -0.827 | Destabilizing | 0.449 | N | 0.495 | neutral | N | 0.479635199 | None | None | N |
| V/K | 0.5691 | likely_pathogenic | 0.5992 | pathogenic | -1.415 | Destabilizing | 0.981 | D | 0.633 | neutral | None | None | None | None | N |
| V/L | 0.4444 | ambiguous | 0.4358 | ambiguous | -0.827 | Destabilizing | 0.29 | N | 0.491 | neutral | N | 0.472422423 | None | None | N |
| V/M | 0.2247 | likely_benign | 0.2207 | benign | -0.985 | Destabilizing | 0.998 | D | 0.576 | neutral | None | None | None | None | N |
| V/N | 0.5704 | likely_pathogenic | 0.5765 | pathogenic | -1.499 | Destabilizing | 0.884 | D | 0.731 | prob.delet. | None | None | None | None | N |
| V/P | 0.9464 | likely_pathogenic | 0.9565 | pathogenic | -1.083 | Destabilizing | 0.939 | D | 0.674 | neutral | None | None | None | None | N |
| V/Q | 0.5372 | ambiguous | 0.5599 | ambiguous | -1.669 | Destabilizing | 0.987 | D | 0.685 | prob.neutral | None | None | None | None | N |
| V/R | 0.4778 | ambiguous | 0.5252 | ambiguous | -0.979 | Destabilizing | 0.991 | D | 0.743 | deleterious | None | None | None | None | N |
| V/S | 0.3824 | ambiguous | 0.3775 | ambiguous | -2.008 | Highly Destabilizing | 0.894 | D | 0.57 | neutral | None | None | None | None | N |
| V/T | 0.2178 | likely_benign | 0.2048 | benign | -1.846 | Destabilizing | 0.037 | N | 0.223 | neutral | None | None | None | None | N |
| V/W | 0.9447 | likely_pathogenic | 0.9518 | pathogenic | -1.634 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| V/Y | 0.7888 | likely_pathogenic | 0.8128 | pathogenic | -1.287 | Destabilizing | 0.999 | D | 0.659 | 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.