TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29672	89239;89240;89241	chr2:178554097;178554096;178554095	chr2:179418824;179418823;179418822
N2AB	28031	84316;84317;84318	chr2:178554097;178554096;178554095	chr2:179418824;179418823;179418822
N2A	27104	81535;81536;81537	chr2:178554097;178554096;178554095	chr2:179418824;179418823;179418822
N2B	20607	62044;62045;62046	chr2:178554097;178554096;178554095	chr2:179418824;179418823;179418822
Novex-1	20732	62419;62420;62421	chr2:178554097;178554096;178554095	chr2:179418824;179418823;179418822
Novex-2	20799	62620;62621;62622	chr2:178554097;178554096;178554095	chr2:179418824;179418823;179418822
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-104
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.1311
• 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/N	None	None	0.83	N	0.831	0.353	0.309839678437	gnomAD-4.0.0	1.59118E-06	None	None	None	None	N	None	5.65611E-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
K/A	0.9512	likely_pathogenic	0.9721	pathogenic	-1.484	Destabilizing	0.648	D	0.664	neutral	None	None	None	None	N
K/C	0.8887	likely_pathogenic	0.9135	pathogenic	-1.561	Destabilizing	0.993	D	0.801	deleterious	None	None	None	None	N
K/D	0.9952	likely_pathogenic	0.9971	pathogenic	-2.693	Highly Destabilizing	0.866	D	0.791	deleterious	None	None	None	None	N
K/E	0.8993	likely_pathogenic	0.9419	pathogenic	-2.368	Highly Destabilizing	0.41	N	0.698	prob.neutral	N	0.48965085	None	None	N
K/F	0.9664	likely_pathogenic	0.9801	pathogenic	-0.827	Destabilizing	0.98	D	0.825	deleterious	None	None	None	None	N
K/G	0.9626	likely_pathogenic	0.9775	pathogenic	-1.931	Destabilizing	0.866	D	0.737	prob.delet.	None	None	None	None	N
K/H	0.7406	likely_pathogenic	0.801	pathogenic	-1.499	Destabilizing	0.98	D	0.808	deleterious	None	None	None	None	N
K/I	0.8349	likely_pathogenic	0.8828	pathogenic	-0.179	Destabilizing	0.908	D	0.834	deleterious	N	0.514419776	None	None	N
K/L	0.8077	likely_pathogenic	0.8474	pathogenic	-0.179	Destabilizing	0.866	D	0.737	prob.delet.	None	None	None	None	N
K/M	0.6207	likely_pathogenic	0.713	pathogenic	-0.641	Destabilizing	0.993	D	0.802	deleterious	None	None	None	None	N
K/N	0.9746	likely_pathogenic	0.9859	pathogenic	-2.233	Highly Destabilizing	0.83	D	0.831	deleterious	N	0.507590521	None	None	N
K/P	0.9982	likely_pathogenic	0.9989	pathogenic	-0.601	Destabilizing	0.929	D	0.811	deleterious	None	None	None	None	N
K/Q	0.4632	ambiguous	0.5914	pathogenic	-1.793	Destabilizing	0.83	D	0.83	deleterious	N	0.473357021	None	None	N
K/R	0.1073	likely_benign	0.1108	benign	-0.957	Destabilizing	0.01	N	0.448	neutral	N	0.429995813	None	None	N
K/S	0.969	likely_pathogenic	0.9841	pathogenic	-2.564	Highly Destabilizing	0.648	D	0.729	prob.delet.	None	None	None	None	N
K/T	0.8658	likely_pathogenic	0.925	pathogenic	-1.996	Destabilizing	0.83	D	0.765	deleterious	N	0.499739708	None	None	N
K/V	0.807	likely_pathogenic	0.8589	pathogenic	-0.601	Destabilizing	0.866	D	0.784	deleterious	None	None	None	None	N
K/W	0.9498	likely_pathogenic	0.9667	pathogenic	-0.947	Destabilizing	0.993	D	0.78	deleterious	None	None	None	None	N
K/Y	0.8844	likely_pathogenic	0.922	pathogenic	-0.62	Destabilizing	0.929	D	0.825	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.