TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29102	87529;87530;87531	chr2:178558050;178558049;178558048	chr2:179422777;179422776;179422775
N2AB	27461	82606;82607;82608	chr2:178558050;178558049;178558048	chr2:179422777;179422776;179422775
N2A	26534	79825;79826;79827	chr2:178558050;178558049;178558048	chr2:179422777;179422776;179422775
N2B	20037	60334;60335;60336	chr2:178558050;178558049;178558048	chr2:179422777;179422776;179422775
Novex-1	20162	60709;60710;60711	chr2:178558050;178558049;178558048	chr2:179422777;179422776;179422775
Novex-2	20229	60910;60911;60912	chr2:178558050;178558049;178558048	chr2:179422777;179422776;179422775
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: Ig-145
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.1099
• 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
I/V	rs1396193875	-1.469	0.011	N	0.226	0.063	0.215869574891	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
I/V	rs1396193875	-1.469	0.011	N	0.226	0.063	0.215869574891	gnomAD-4.0.0	1.591E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85776E-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	0.8966	likely_pathogenic	0.871	pathogenic	-3.061	Highly Destabilizing	0.845	D	0.704	prob.neutral	None	None	None	None	N
I/C	0.8966	likely_pathogenic	0.8743	pathogenic	-2.753	Highly Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
I/D	0.9982	likely_pathogenic	0.9967	pathogenic	-3.75	Highly Destabilizing	0.996	D	0.855	deleterious	None	None	None	None	N
I/E	0.9955	likely_pathogenic	0.9924	pathogenic	-3.449	Highly Destabilizing	0.987	D	0.849	deleterious	None	None	None	None	N
I/F	0.3501	ambiguous	0.2789	benign	-1.876	Destabilizing	0.967	D	0.636	neutral	N	0.440316302	None	None	N
I/G	0.9851	likely_pathogenic	0.9782	pathogenic	-3.692	Highly Destabilizing	0.987	D	0.847	deleterious	None	None	None	None	N
I/H	0.9906	likely_pathogenic	0.9838	pathogenic	-3.268	Highly Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
I/K	0.9924	likely_pathogenic	0.9856	pathogenic	-2.608	Highly Destabilizing	0.987	D	0.851	deleterious	None	None	None	None	N
I/L	0.1594	likely_benign	0.1478	benign	-1.181	Destabilizing	0.426	N	0.436	neutral	N	0.345660544	None	None	N
I/M	0.2013	likely_benign	0.1791	benign	-1.371	Destabilizing	0.983	D	0.62	neutral	N	0.4918412	None	None	N
I/N	0.9833	likely_pathogenic	0.9734	pathogenic	-3.226	Highly Destabilizing	0.994	D	0.849	deleterious	N	0.456630393	None	None	N
I/P	0.9961	likely_pathogenic	0.994	pathogenic	-1.796	Destabilizing	0.996	D	0.852	deleterious	None	None	None	None	N
I/Q	0.9912	likely_pathogenic	0.9843	pathogenic	-2.942	Highly Destabilizing	0.996	D	0.857	deleterious	None	None	None	None	N
I/R	0.9861	likely_pathogenic	0.9744	pathogenic	-2.432	Highly Destabilizing	0.987	D	0.855	deleterious	None	None	None	None	N
I/S	0.9742	likely_pathogenic	0.9626	pathogenic	-3.917	Highly Destabilizing	0.967	D	0.793	deleterious	N	0.456630393	None	None	N
I/T	0.9626	likely_pathogenic	0.946	pathogenic	-3.443	Highly Destabilizing	0.892	D	0.721	prob.delet.	N	0.456630393	None	None	N
I/V	0.0838	likely_benign	0.0867	benign	-1.796	Destabilizing	0.011	N	0.226	neutral	N	0.483683077	None	None	N
I/W	0.957	likely_pathogenic	0.929	pathogenic	-2.323	Highly Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
I/Y	0.8886	likely_pathogenic	0.8358	pathogenic	-2.112	Highly Destabilizing	0.987	D	0.709	prob.delet.	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.