TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7127	21604;21605;21606	chr2:178723880;178723879;178723878	chr2:179588607;179588606;179588605
N2AB	6810	20653;20654;20655	chr2:178723880;178723879;178723878	chr2:179588607;179588606;179588605
N2A	5883	17872;17873;17874	chr2:178723880;178723879;178723878	chr2:179588607;179588606;179588605
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: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-55
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.0939
• 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	None	None	0.028	N	0.675	0.315	0.742840689568	gnomAD-4.0.0	1.44039E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.575E-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
C/A	0.6402	likely_pathogenic	0.6015	pathogenic	-1.924	Destabilizing	0.525	D	0.654	neutral	None	None	None	None	N
C/D	0.8943	likely_pathogenic	0.8639	pathogenic	-1.314	Destabilizing	0.949	D	0.809	deleterious	None	None	None	None	N
C/E	0.9647	likely_pathogenic	0.9546	pathogenic	-1.155	Destabilizing	0.949	D	0.807	deleterious	None	None	None	None	N
C/F	0.7063	likely_pathogenic	0.6727	pathogenic	-1.16	Destabilizing	0.966	D	0.791	deleterious	N	0.498138725	None	None	N
C/G	0.3549	ambiguous	0.3159	benign	-2.258	Highly Destabilizing	0.801	D	0.792	deleterious	N	0.495834547	None	None	N
C/H	0.9318	likely_pathogenic	0.917	pathogenic	-2.342	Highly Destabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
C/I	0.8523	likely_pathogenic	0.8384	pathogenic	-1.038	Destabilizing	0.949	D	0.805	deleterious	None	None	None	None	N
C/K	0.9878	likely_pathogenic	0.984	pathogenic	-1.547	Destabilizing	0.728	D	0.788	deleterious	None	None	None	None	N
C/L	0.8133	likely_pathogenic	0.7892	pathogenic	-1.038	Destabilizing	0.728	D	0.709	prob.delet.	None	None	None	None	N
C/M	0.855	likely_pathogenic	0.8307	pathogenic	0.008	Stabilizing	0.998	D	0.77	deleterious	None	None	None	None	N
C/N	0.7957	likely_pathogenic	0.7516	pathogenic	-1.725	Destabilizing	0.949	D	0.808	deleterious	None	None	None	None	N
C/P	0.9973	likely_pathogenic	0.9964	pathogenic	-1.31	Destabilizing	0.974	D	0.827	deleterious	None	None	None	None	N
C/Q	0.948	likely_pathogenic	0.9344	pathogenic	-1.504	Destabilizing	0.949	D	0.829	deleterious	None	None	None	None	N
C/R	0.9374	likely_pathogenic	0.9243	pathogenic	-1.536	Destabilizing	0.028	N	0.675	neutral	N	0.484705278	None	None	N
C/S	0.4078	ambiguous	0.3547	ambiguous	-2.178	Highly Destabilizing	0.669	D	0.738	prob.delet.	N	0.480915783	None	None	N
C/T	0.4803	ambiguous	0.4457	ambiguous	-1.848	Destabilizing	0.067	N	0.52	neutral	None	None	None	None	N
C/V	0.726	likely_pathogenic	0.7067	pathogenic	-1.31	Destabilizing	0.728	D	0.731	prob.delet.	None	None	None	None	N
C/W	0.9206	likely_pathogenic	0.9039	pathogenic	-1.354	Destabilizing	0.997	D	0.769	deleterious	N	0.512724261	None	None	N
C/Y	0.8241	likely_pathogenic	0.7914	pathogenic	-1.287	Destabilizing	0.989	D	0.784	deleterious	N	0.498392215	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.