TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7220	21883;21884;21885	chr2:178723442;178723441;178723440	chr2:179588169;179588168;179588167
N2AB	6903	20932;20933;20934	chr2:178723442;178723441;178723440	chr2:179588169;179588168;179588167
N2A	5976	18151;18152;18153	chr2:178723442;178723441;178723440	chr2:179588169;179588168;179588167
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-56
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.1063
• 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/Y	None	None	1.0	N	0.877	0.439	0.809519752258	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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
C/A	0.5016	ambiguous	0.5308	ambiguous	-1.726	Destabilizing	0.998	D	0.64	neutral	None	None	None	None	N
C/D	0.8516	likely_pathogenic	0.8839	pathogenic	-0.142	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
C/E	0.917	likely_pathogenic	0.9457	pathogenic	-0.055	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
C/F	0.333	likely_benign	0.426	ambiguous	-1.117	Destabilizing	1.0	D	0.881	deleterious	N	0.497809557	None	None	N
C/G	0.2796	likely_benign	0.3064	benign	-2.021	Highly Destabilizing	1.0	D	0.827	deleterious	D	0.533366188	None	None	N
C/H	0.6463	likely_pathogenic	0.7368	pathogenic	-1.975	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
C/I	0.6774	likely_pathogenic	0.7395	pathogenic	-0.973	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
C/K	0.8628	likely_pathogenic	0.9138	pathogenic	-0.813	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
C/L	0.6483	likely_pathogenic	0.7039	pathogenic	-0.973	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
C/M	0.7877	likely_pathogenic	0.8248	pathogenic	-0.115	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
C/N	0.731	likely_pathogenic	0.7736	pathogenic	-0.723	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
C/P	0.9908	likely_pathogenic	0.9929	pathogenic	-1.198	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
C/Q	0.7561	likely_pathogenic	0.8408	pathogenic	-0.667	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
C/R	0.5051	ambiguous	0.6312	pathogenic	-0.666	Destabilizing	1.0	D	0.889	deleterious	N	0.487338625	None	None	N
C/S	0.3407	ambiguous	0.3516	ambiguous	-1.303	Destabilizing	1.0	D	0.779	deleterious	N	0.501925774	None	None	N
C/T	0.5728	likely_pathogenic	0.5958	pathogenic	-1.034	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
C/V	0.5659	likely_pathogenic	0.6289	pathogenic	-1.198	Destabilizing	0.999	D	0.722	prob.delet.	None	None	None	None	N
C/W	0.7375	likely_pathogenic	0.8109	pathogenic	-1.058	Destabilizing	1.0	D	0.839	deleterious	N	0.495442927	None	None	N
C/Y	0.5197	ambiguous	0.6401	pathogenic	-1.056	Destabilizing	1.0	D	0.877	deleterious	N	0.492302602	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.