TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20013	60262;60263;60264	chr2:178591782;178591781;178591780	chr2:179456509;179456508;179456507
N2AB	18372	55339;55340;55341	chr2:178591782;178591781;178591780	chr2:179456509;179456508;179456507
N2A	17445	52558;52559;52560	chr2:178591782;178591781;178591780	chr2:179456509;179456508;179456507
N2B	10948	33067;33068;33069	chr2:178591782;178591781;178591780	chr2:179456509;179456508;179456507
Novex-1	11073	33442;33443;33444	chr2:178591782;178591781;178591780	chr2:179456509;179456508;179456507
Novex-2	11140	33643;33644;33645	chr2:178591782;178591781;178591780	chr2:179456509;179456508;179456507
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-33
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.2244
• 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/S	rs2050262481	None	0.997	N	0.696	0.444	0.789519865058	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
L/S	rs2050262481	None	0.997	N	0.696	0.444	0.789519865058	gnomAD-4.0.0	6.57903E-06	None	None	None	None	N	None	2.41441E-05	0	None	0	0	None	0	0	0	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	0.3007	likely_benign	0.3297	benign	-2.486	Highly Destabilizing	0.966	D	0.539	neutral	None	None	None	None	N
L/C	0.423	ambiguous	0.4493	ambiguous	-1.879	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
L/D	0.7579	likely_pathogenic	0.8089	pathogenic	-2.556	Highly Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
L/E	0.4165	ambiguous	0.4453	ambiguous	-2.436	Highly Destabilizing	0.998	D	0.74	deleterious	None	None	None	None	N
L/F	0.1925	likely_benign	0.1892	benign	-1.562	Destabilizing	0.997	D	0.741	deleterious	N	0.463377667	None	None	N
L/G	0.7142	likely_pathogenic	0.7527	pathogenic	-2.927	Highly Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
L/H	0.2085	likely_benign	0.2383	benign	-2.123	Highly Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
L/I	0.0748	likely_benign	0.0794	benign	-1.257	Destabilizing	0.921	D	0.575	neutral	None	None	None	None	N
L/K	0.3428	ambiguous	0.3804	ambiguous	-1.868	Destabilizing	0.998	D	0.698	prob.neutral	None	None	None	None	N
L/M	0.1133	likely_benign	0.1165	benign	-1.213	Destabilizing	0.997	D	0.761	deleterious	N	0.501069264	None	None	N
L/N	0.4648	ambiguous	0.5307	ambiguous	-1.95	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
L/P	0.9744	likely_pathogenic	0.9803	pathogenic	-1.644	Destabilizing	0.999	D	0.758	deleterious	None	None	None	None	N
L/Q	0.1779	likely_benign	0.1908	benign	-2.012	Highly Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
L/R	0.2277	likely_benign	0.2498	benign	-1.34	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
L/S	0.3481	ambiguous	0.3963	ambiguous	-2.634	Highly Destabilizing	0.997	D	0.696	prob.neutral	N	0.466415186	None	None	N
L/T	0.1896	likely_benign	0.2229	benign	-2.391	Highly Destabilizing	0.995	D	0.689	prob.neutral	None	None	None	None	N
L/V	0.0764	likely_benign	0.0779	benign	-1.644	Destabilizing	0.117	N	0.354	neutral	N	0.414642358	None	None	N
L/W	0.3059	likely_benign	0.3105	benign	-1.771	Destabilizing	1.0	D	0.751	deleterious	N	0.510766183	None	None	N
L/Y	0.3897	ambiguous	0.3991	ambiguous	-1.558	Destabilizing	0.999	D	0.748	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.