TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4873	14842;14843;14844	chr2:178735829;178735828;178735827	chr2:179600556;179600555;179600554
N2AB	4556	13891;13892;13893	chr2:178735829;178735828;178735827	chr2:179600556;179600555;179600554
N2A	3629	11110;11111;11112	chr2:178735829;178735828;178735827	chr2:179600556;179600555;179600554
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: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-31
• Domain position: 79
• Structural Position: 163
• Q(SASA): 0.8474
• 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
F/L	None	None	0.704	N	0.303	0.262	0.304108284078	gnomAD-4.0.0	1.59142E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85816E-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
F/A	0.7601	likely_pathogenic	0.8296	pathogenic	-0.687	Destabilizing	0.079	N	0.354	neutral	None	None	None	None	I
F/C	0.7005	likely_pathogenic	0.7547	pathogenic	-0.275	Destabilizing	0.999	D	0.575	neutral	N	0.51177561	None	None	I
F/D	0.9405	likely_pathogenic	0.9543	pathogenic	0.638	Stabilizing	0.991	D	0.561	neutral	None	None	None	None	I
F/E	0.9613	likely_pathogenic	0.9662	pathogenic	0.601	Stabilizing	0.991	D	0.533	neutral	None	None	None	None	I
F/G	0.9334	likely_pathogenic	0.949	pathogenic	-0.836	Destabilizing	0.939	D	0.545	neutral	None	None	None	None	I
F/H	0.7775	likely_pathogenic	0.7894	pathogenic	0.333	Stabilizing	0.999	D	0.535	neutral	None	None	None	None	I
F/I	0.622	likely_pathogenic	0.6724	pathogenic	-0.33	Destabilizing	0.704	D	0.38	neutral	N	0.450443854	None	None	I
F/K	0.9676	likely_pathogenic	0.9713	pathogenic	-0.01	Destabilizing	0.991	D	0.543	neutral	None	None	None	None	I
F/L	0.9615	likely_pathogenic	0.968	pathogenic	-0.33	Destabilizing	0.704	D	0.303	neutral	N	0.406339391	None	None	I
F/M	0.8414	likely_pathogenic	0.8632	pathogenic	-0.374	Destabilizing	0.991	D	0.427	neutral	None	None	None	None	I
F/N	0.8509	likely_pathogenic	0.8793	pathogenic	-0.017	Destabilizing	0.997	D	0.563	neutral	None	None	None	None	I
F/P	0.9973	likely_pathogenic	0.998	pathogenic	-0.43	Destabilizing	0.991	D	0.56	neutral	None	None	None	None	I
F/Q	0.9367	likely_pathogenic	0.9457	pathogenic	-0.045	Destabilizing	0.997	D	0.555	neutral	None	None	None	None	I
F/R	0.9179	likely_pathogenic	0.9282	pathogenic	0.343	Stabilizing	0.991	D	0.565	neutral	None	None	None	None	I
F/S	0.7191	likely_pathogenic	0.796	pathogenic	-0.578	Destabilizing	0.852	D	0.547	neutral	N	0.475279692	None	None	I
F/T	0.8571	likely_pathogenic	0.893	pathogenic	-0.525	Destabilizing	0.939	D	0.549	neutral	None	None	None	None	I
F/V	0.5619	ambiguous	0.6202	pathogenic	-0.43	Destabilizing	0.061	N	0.313	neutral	N	0.428213776	None	None	I
F/W	0.6647	likely_pathogenic	0.6658	pathogenic	-0.357	Destabilizing	0.999	D	0.457	neutral	None	None	None	None	I
F/Y	0.2124	likely_benign	0.1907	benign	-0.29	Destabilizing	0.986	D	0.39	neutral	N	0.398330804	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.