TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6967	21124;21125;21126	chr2:178724476;178724475;178724474	chr2:179589203;179589202;179589201
N2AB	6650	20173;20174;20175	chr2:178724476;178724475;178724474	chr2:179589203;179589202;179589201
N2A	5723	17392;17393;17394	chr2:178724476;178724475;178724474	chr2:179589203;179589202;179589201
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: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-54
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.1557
• 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
L/V	None	None	0.025	D	0.357	0.248	0.119812018005	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
L/A	0.865	likely_pathogenic	0.7765	pathogenic	-2.634	Highly Destabilizing	0.845	D	0.718	prob.delet.	None	None	None	None	N
L/C	0.9431	likely_pathogenic	0.9132	pathogenic	-2.049	Highly Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
L/D	0.9986	likely_pathogenic	0.9975	pathogenic	-2.942	Highly Destabilizing	0.996	D	0.865	deleterious	None	None	None	None	N
L/E	0.9862	likely_pathogenic	0.9768	pathogenic	-2.675	Highly Destabilizing	0.987	D	0.875	deleterious	None	None	None	None	N
L/F	0.261	likely_benign	0.2109	benign	-1.56	Destabilizing	0.975	D	0.724	prob.delet.	None	None	None	None	N
L/G	0.9821	likely_pathogenic	0.9714	pathogenic	-3.231	Highly Destabilizing	0.987	D	0.873	deleterious	None	None	None	None	N
L/H	0.9671	likely_pathogenic	0.9504	pathogenic	-2.7	Highly Destabilizing	0.999	D	0.852	deleterious	None	None	None	None	N
L/I	0.1611	likely_benign	0.1322	benign	-0.883	Destabilizing	0.033	N	0.359	neutral	None	None	None	None	N
L/K	0.9799	likely_pathogenic	0.9652	pathogenic	-2.001	Highly Destabilizing	0.975	D	0.856	deleterious	None	None	None	None	N
L/M	0.1956	likely_benign	0.138	benign	-0.931	Destabilizing	0.63	D	0.521	neutral	D	0.543430943	None	None	N
L/N	0.9931	likely_pathogenic	0.9876	pathogenic	-2.426	Highly Destabilizing	0.987	D	0.877	deleterious	None	None	None	None	N
L/P	0.9913	likely_pathogenic	0.9878	pathogenic	-1.45	Destabilizing	0.994	D	0.865	deleterious	D	0.621952597	None	None	N
L/Q	0.9489	likely_pathogenic	0.9109	pathogenic	-2.218	Highly Destabilizing	0.983	D	0.857	deleterious	D	0.621952597	None	None	N
L/R	0.9566	likely_pathogenic	0.9351	pathogenic	-1.857	Destabilizing	0.967	D	0.854	deleterious	D	0.621952597	None	None	N
L/S	0.976	likely_pathogenic	0.9522	pathogenic	-3.164	Highly Destabilizing	0.975	D	0.847	deleterious	None	None	None	None	N
L/T	0.9114	likely_pathogenic	0.8309	pathogenic	-2.728	Highly Destabilizing	0.975	D	0.788	deleterious	None	None	None	None	N
L/V	0.2019	likely_benign	0.1446	benign	-1.45	Destabilizing	0.025	N	0.357	neutral	D	0.55524098	None	None	N
L/W	0.7689	likely_pathogenic	0.6984	pathogenic	-1.926	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
L/Y	0.8933	likely_pathogenic	0.8502	pathogenic	-1.654	Destabilizing	0.987	D	0.756	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.