Isoform Positions

Isoform Protein Position Transcript Position Chromosomal Position (HG38) Chromosomal Position (HG19)
IC3171295359;95360;95361 chr2:178546102;178546101;178546100chr2:179410829;179410828;179410827
N2AB3007190436;90437;90438 chr2:178546102;178546101;178546100chr2:179410829;179410828;179410827
N2A2914487655;87656;87657 chr2:178546102;178546101;178546100chr2:179410829;179410828;179410827
N2B2264768164;68165;68166 chr2:178546102;178546101;178546100chr2:179410829;179410828;179410827
Novex-12277268539;68540;68541 chr2:178546102;178546101;178546100chr2:179410829;179410828;179410827
Novex-22283968740;68741;68742 chr2:178546102;178546101;178546100chr2:179410829;179410828;179410827
Novex-3NoneNone chr2:Nonechr2:None

Information

  • RefSeq wild type amino acid: C
  • RefSeq wild type transcript codon: TGT
  • RefSeq wild type template codon: ACA
  • Domain: Fn3-119
  • Domain position: 5
  • Structural Position: 5
  • Q(SASA): 0.1205
  • Predicted PPI site: N

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
C/R rs869320740 -1.28 0.996 N 0.743 0.791 0.637424115254 gnomAD-2.1.1 4.11E-06 None None None None N None 0 0 None 0 0 None 0 None 0 9.1E-06 0
C/R rs869320740 -1.28 0.996 N 0.743 0.791 0.637424115254 Pfeffer (2012) Ohlsson (2012) Toro (2013) Palmio (2013) Pfeffer (2014) Hedberg (2014) Uruha (2015) Yue (2015) Palmio (2019) Morais (2020) Huang (2021) None MFM HMERF het None None N Found in multiple studies with full penetrance; WES prioritisation in single family; co-segregates in 3 families tested; WES/WGS prioritisation in 12 HMERF families, full penetrance; Genetic analysis of genes in 127 undiagnosed patients, likely MFM; Genetic analysis of genes in 12 HMERF families; WES prioritisation of single US family + 45 unrelated probands; Genetic analysis of Fn3-119 in 187 MFM patients to assess diagnostic value of sub-sarcolemmal necklace alignments of cytoplasmic bodies for HMERF; Genetic analysis of CN patient (familial) None None None None None None None None None None None
C/R rs869320740 -1.28 0.996 N 0.743 0.791 0.637424115254 gnomAD-4.0.0 3.43489E-06 None None None None N None 0 0 None 0 0 None 1.88501E-05 0 2.7073E-06 0 1.66301E-05
C/W None None 0.999 N 0.679 0.399 0.343101102393 Yeo (2021) None HMERF het None None N Genetic analysis of single KR family with HMERF; co-segregates with condition (n = 2, 2 affected (total 2), 2 predeceased with similar pathology) None None None None None None None None None None None
C/Y None -1.682 0.996 N 0.674 0.723 0.515430650102 Uruha (2015) None MFM HMERF het None None N Genetic analysis of Fn3-119 in 187 MFM patients to assess diagnostic value of sub-sarcolemmal necklace alignments of cytoplasmic bodies for HMERF None None None None None None None None None None None

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
C/A 0.3542 ambiguous 0.4566 ambiguous -1.596 Destabilizing 0.863 D 0.555 neutral None None None None N
C/D 0.8846 likely_pathogenic 0.9559 pathogenic -1.394 Destabilizing 0.991 D 0.732 prob.delet. None None None None N
C/E 0.9103 likely_pathogenic 0.9681 pathogenic -1.237 Destabilizing 0.991 D 0.733 prob.delet. None None None None N
C/F 0.5883 likely_pathogenic 0.7073 pathogenic -1.063 Destabilizing 0.996 D 0.679 prob.neutral N 0.504122638 None None N
C/G 0.3064 likely_benign 0.4499 ambiguous -1.924 Destabilizing 0.959 D 0.715 prob.delet. N 0.474839881 None None N
C/H 0.9051 likely_pathogenic 0.9577 pathogenic -2.247 Highly Destabilizing 0.999 D 0.712 prob.delet. None None None None N
C/I 0.4633 ambiguous 0.5261 ambiguous -0.743 Destabilizing 0.997 D 0.709 prob.delet. None None None None N
C/K 0.9651 likely_pathogenic 0.9871 pathogenic -1.204 Destabilizing 0.991 D 0.732 prob.delet. None None None None N
C/L 0.5036 ambiguous 0.5875 pathogenic -0.743 Destabilizing 0.969 D 0.665 neutral None None None None N
C/M 0.7183 likely_pathogenic 0.7929 pathogenic 0.119 Stabilizing 0.997 D 0.649 neutral None None None None N
C/N 0.7989 likely_pathogenic 0.8968 pathogenic -1.457 Destabilizing 0.997 D 0.746 deleterious None None None None N
C/P 0.3731 ambiguous 0.3913 ambiguous -1.002 Destabilizing 0.02 N 0.6 neutral None None None None N
C/Q 0.898 likely_pathogenic 0.9558 pathogenic -1.254 Destabilizing 0.997 D 0.741 deleterious None None None None N
C/R 0.8445 likely_pathogenic 0.9364 pathogenic -1.338 Destabilizing 0.996 D 0.743 deleterious N 0.504295996 None None N
C/S 0.4314 ambiguous 0.5738 pathogenic -1.803 Destabilizing 0.959 D 0.685 prob.neutral N 0.431126389 None None N
C/T 0.52 ambiguous 0.6172 pathogenic -1.472 Destabilizing 0.969 D 0.679 prob.neutral None None None None N
C/V 0.3137 likely_benign 0.3569 ambiguous -1.002 Destabilizing 0.969 D 0.681 prob.neutral None None None None N
C/W 0.8964 likely_pathogenic 0.9503 pathogenic -1.323 Destabilizing 0.999 D 0.679 prob.neutral N 0.504642713 None None N
C/Y 0.7862 likely_pathogenic 0.8868 pathogenic -1.158 Destabilizing 0.996 D 0.674 neutral N 0.504295996 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.