TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20009	60250;60251;60252	chr2:178591794;178591793;178591792	chr2:179456521;179456520;179456519
N2AB	18368	55327;55328;55329	chr2:178591794;178591793;178591792	chr2:179456521;179456520;179456519
N2A	17441	52546;52547;52548	chr2:178591794;178591793;178591792	chr2:179456521;179456520;179456519
N2B	10944	33055;33056;33057	chr2:178591794;178591793;178591792	chr2:179456521;179456520;179456519
Novex-1	11069	33430;33431;33432	chr2:178591794;178591793;178591792	chr2:179456521;179456520;179456519
Novex-2	11136	33631;33632;33633	chr2:178591794;178591793;178591792	chr2:179456521;179456520;179456519
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-33
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1987
• Predicted PPI site: I

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
I/V	rs371988490	-1.495	0.993	N	0.392	0.277	None	gnomAD-2.1.1	1.43E-05	None	None	None	None	I	None	1.65344E-04	0	None	0	0	None	0	None	0	0	0
I/V	rs371988490	-1.495	0.993	N	0.392	0.277	None	gnomAD-3.1.2	5.92E-05	None	None	None	None	I	None	2.17161E-04	0	0	0	0	None	0	0	0	0	0
I/V	rs371988490	-1.495	0.993	N	0.392	0.277	None	gnomAD-4.0.0	1.66646E-05	None	None	None	None	I	None	1.86094E-04	0	None	0	0	None	0	0	4.78826E-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
I/A	0.9645	likely_pathogenic	0.9712	pathogenic	-2.321	Highly Destabilizing	0.999	D	0.653	neutral	None	None	None	None	I
I/C	0.9705	likely_pathogenic	0.9812	pathogenic	-1.495	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
I/D	0.9982	likely_pathogenic	0.9987	pathogenic	-2.27	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
I/E	0.9929	likely_pathogenic	0.9942	pathogenic	-2.186	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
I/F	0.9148	likely_pathogenic	0.9352	pathogenic	-1.613	Destabilizing	1.0	D	0.828	deleterious	N	0.516636784	None	None	I
I/G	0.9961	likely_pathogenic	0.997	pathogenic	-2.747	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
I/H	0.9951	likely_pathogenic	0.9966	pathogenic	-2.066	Highly Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
I/K	0.9857	likely_pathogenic	0.9878	pathogenic	-1.722	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
I/L	0.356	ambiguous	0.36	ambiguous	-1.156	Destabilizing	0.993	D	0.407	neutral	N	0.51881245	None	None	I
I/M	0.5494	ambiguous	0.5983	pathogenic	-0.856	Destabilizing	1.0	D	0.801	deleterious	D	0.525919629	None	None	I
I/N	0.9686	likely_pathogenic	0.9785	pathogenic	-1.685	Destabilizing	1.0	D	0.86	deleterious	N	0.50636057	None	None	I
I/P	0.9689	likely_pathogenic	0.9733	pathogenic	-1.519	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	I
I/Q	0.9891	likely_pathogenic	0.9914	pathogenic	-1.784	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	I
I/R	0.9798	likely_pathogenic	0.9835	pathogenic	-1.153	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	I
I/S	0.9792	likely_pathogenic	0.9851	pathogenic	-2.334	Highly Destabilizing	1.0	D	0.852	deleterious	N	0.514816813	None	None	I
I/T	0.9493	likely_pathogenic	0.9582	pathogenic	-2.125	Highly Destabilizing	1.0	D	0.819	deleterious	N	0.503295924	None	None	I
I/V	0.0925	likely_benign	0.0826	benign	-1.519	Destabilizing	0.993	D	0.392	neutral	N	0.449797869	None	None	I
I/W	0.9977	likely_pathogenic	0.9984	pathogenic	-1.839	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
I/Y	0.9882	likely_pathogenic	0.9923	pathogenic	-1.612	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I

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.