TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27508	82747;82748;82749	chr2:178563610;178563609;178563608	chr2:179428337;179428336;179428335
N2AB	25867	77824;77825;77826	chr2:178563610;178563609;178563608	chr2:179428337;179428336;179428335
N2A	24940	75043;75044;75045	chr2:178563610;178563609;178563608	chr2:179428337;179428336;179428335
N2B	18443	55552;55553;55554	chr2:178563610;178563609;178563608	chr2:179428337;179428336;179428335
Novex-1	18568	55927;55928;55929	chr2:178563610;178563609;178563608	chr2:179428337;179428336;179428335
Novex-2	18635	56128;56129;56130	chr2:178563610;178563609;178563608	chr2:179428337;179428336;179428335
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: Fn3-88
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.2157
• 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	rs766900644	-1.949	0.988	D	0.81	0.34	0.284539287134	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
K/N	rs766900644	-1.949	0.988	D	0.81	0.34	0.284539287134	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
K/N	rs766900644	-1.949	0.988	D	0.81	0.34	0.284539287134	gnomAD-4.0.0	2.4789E-06	None	None	None	None	N	None	0	1.66744E-05	None	0	0	None	0	0	2.54287E-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
K/A	0.9779	likely_pathogenic	0.9761	pathogenic	-1.353	Destabilizing	0.968	D	0.703	prob.neutral	None	None	None	None	N
K/C	0.9278	likely_pathogenic	0.924	pathogenic	-1.373	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
K/D	0.998	likely_pathogenic	0.9978	pathogenic	-1.852	Destabilizing	0.995	D	0.836	deleterious	None	None	None	None	N
K/E	0.9592	likely_pathogenic	0.9568	pathogenic	-1.535	Destabilizing	0.958	D	0.679	prob.neutral	N	0.50874261	None	None	N
K/F	0.9834	likely_pathogenic	0.9845	pathogenic	-0.595	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
K/G	0.9803	likely_pathogenic	0.9815	pathogenic	-1.86	Destabilizing	0.991	D	0.792	deleterious	None	None	None	None	N
K/H	0.8251	likely_pathogenic	0.8342	pathogenic	-1.662	Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	N
K/I	0.9226	likely_pathogenic	0.907	pathogenic	0.091	Stabilizing	0.994	D	0.859	deleterious	N	0.513072982	None	None	N
K/L	0.8605	likely_pathogenic	0.8499	pathogenic	0.091	Stabilizing	0.991	D	0.792	deleterious	None	None	None	None	N
K/M	0.7415	likely_pathogenic	0.7117	pathogenic	-0.239	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
K/N	0.9883	likely_pathogenic	0.9873	pathogenic	-1.838	Destabilizing	0.988	D	0.81	deleterious	D	0.531455221	None	None	N
K/P	0.9993	likely_pathogenic	0.9992	pathogenic	-0.369	Destabilizing	0.998	D	0.843	deleterious	None	None	None	None	N
K/Q	0.6543	likely_pathogenic	0.6398	pathogenic	-1.45	Destabilizing	0.988	D	0.813	deleterious	N	0.489321682	None	None	N
K/R	0.113	likely_benign	0.1199	benign	-0.875	Destabilizing	0.142	N	0.371	neutral	N	0.466628616	None	None	N
K/S	0.9864	likely_pathogenic	0.9858	pathogenic	-2.383	Highly Destabilizing	0.968	D	0.725	prob.delet.	None	None	None	None	N
K/T	0.9467	likely_pathogenic	0.9419	pathogenic	-1.79	Destabilizing	0.988	D	0.804	deleterious	N	0.490852165	None	None	N
K/V	0.897	likely_pathogenic	0.8799	pathogenic	-0.369	Destabilizing	0.995	D	0.827	deleterious	None	None	None	None	N
K/W	0.9671	likely_pathogenic	0.9744	pathogenic	-0.641	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
K/Y	0.9224	likely_pathogenic	0.9267	pathogenic	-0.29	Destabilizing	0.998	D	0.86	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.