TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3092	9499;9500;9501	chr2:178768045;178768044;178768043	chr2:179632772;179632771;179632770
N2AB	3092	9499;9500;9501	chr2:178768045;178768044;178768043	chr2:179632772;179632771;179632770
N2A	3092	9499;9500;9501	chr2:178768045;178768044;178768043	chr2:179632772;179632771;179632770
N2B	3046	9361;9362;9363	chr2:178768045;178768044;178768043	chr2:179632772;179632771;179632770
Novex-1	3046	9361;9362;9363	chr2:178768045;178768044;178768043	chr2:179632772;179632771;179632770
Novex-2	3046	9361;9362;9363	chr2:178768045;178768044;178768043	chr2:179632772;179632771;179632770
Novex-3	3092	9499;9500;9501	chr2:178768045;178768044;178768043	chr2:179632772;179632771;179632770

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-21
• Domain position: 35
• Structural Position: 50
• Q(SASA): 0.1887
• 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
K/Q	None	None	1.0	N	0.669	0.426	0.130388298395	gnomAD-4.0.0	1.59052E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	0
K/R	None	None	0.999	N	0.599	0.349	0.154104182512	gnomAD-4.0.0	1.32035E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.44375E-05	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
K/A	0.9815	likely_pathogenic	0.9777	pathogenic	-0.962	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
K/C	0.9832	likely_pathogenic	0.9816	pathogenic	-1.059	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
K/D	0.9974	likely_pathogenic	0.9966	pathogenic	-0.43	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
K/E	0.9556	likely_pathogenic	0.9409	pathogenic	-0.275	Destabilizing	0.999	D	0.593	neutral	D	0.580682362	None	None	N
K/F	0.9927	likely_pathogenic	0.9885	pathogenic	-0.674	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
K/G	0.9944	likely_pathogenic	0.9917	pathogenic	-1.357	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
K/H	0.8438	likely_pathogenic	0.8107	pathogenic	-1.706	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
K/I	0.9153	likely_pathogenic	0.9108	pathogenic	0.085	Stabilizing	1.0	D	0.825	deleterious	D	0.579407856	None	None	N
K/L	0.9057	likely_pathogenic	0.8952	pathogenic	0.085	Stabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
K/M	0.8333	likely_pathogenic	0.815	pathogenic	None	Stabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
K/N	0.9873	likely_pathogenic	0.982	pathogenic	-0.824	Destabilizing	1.0	D	0.689	prob.neutral	D	0.547446683	None	None	N
K/P	0.9993	likely_pathogenic	0.9989	pathogenic	-0.235	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
K/Q	0.7601	likely_pathogenic	0.7176	pathogenic	-0.855	Destabilizing	1.0	D	0.669	neutral	N	0.490012089	None	None	N
K/R	0.168	likely_benign	0.1587	benign	-0.752	Destabilizing	0.999	D	0.599	neutral	N	0.358441712	None	None	N
K/S	0.993	likely_pathogenic	0.9908	pathogenic	-1.567	Destabilizing	0.999	D	0.61	neutral	None	None	None	None	N
K/T	0.9685	likely_pathogenic	0.9636	pathogenic	-1.183	Destabilizing	1.0	D	0.746	deleterious	D	0.58049833	None	None	N
K/V	0.8917	likely_pathogenic	0.8895	pathogenic	-0.235	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
K/W	0.989	likely_pathogenic	0.9841	pathogenic	-0.523	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
K/Y	0.9723	likely_pathogenic	0.962	pathogenic	-0.194	Destabilizing	1.0	D	0.787	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.