TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18030	54313;54314;54315	chr2:178605089;178605088;178605087	chr2:179469816;179469815;179469814
N2AB	16389	49390;49391;49392	chr2:178605089;178605088;178605087	chr2:179469816;179469815;179469814
N2A	15462	46609;46610;46611	chr2:178605089;178605088;178605087	chr2:179469816;179469815;179469814
N2B	8965	27118;27119;27120	chr2:178605089;178605088;178605087	chr2:179469816;179469815;179469814
Novex-1	9090	27493;27494;27495	chr2:178605089;178605088;178605087	chr2:179469816;179469815;179469814
Novex-2	9157	27694;27695;27696	chr2:178605089;178605088;178605087	chr2:179469816;179469815;179469814
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-114
• Domain position: 63
• Structural Position: 138
• Q(SASA): 0.0823
• 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/F	None	None	0.864	N	0.593	0.504	0.532744658726	gnomAD-4.0.0	1.3692E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79975E-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
L/A	0.8025	likely_pathogenic	0.8951	pathogenic	-2.572	Highly Destabilizing	0.547	D	0.742	deleterious	None	None	None	None	N
L/C	0.765	likely_pathogenic	0.8851	pathogenic	-2.043	Highly Destabilizing	0.985	D	0.744	deleterious	None	None	None	None	N
L/D	0.9989	likely_pathogenic	0.9995	pathogenic	-3.504	Highly Destabilizing	0.981	D	0.871	deleterious	None	None	None	None	N
L/E	0.9937	likely_pathogenic	0.9968	pathogenic	-3.198	Highly Destabilizing	0.945	D	0.862	deleterious	None	None	None	None	N
L/F	0.3155	likely_benign	0.4752	ambiguous	-1.642	Destabilizing	0.864	D	0.593	neutral	N	0.493719224	None	None	N
L/G	0.9696	likely_pathogenic	0.9871	pathogenic	-3.17	Highly Destabilizing	0.945	D	0.857	deleterious	None	None	None	None	N
L/H	0.9814	likely_pathogenic	0.9914	pathogenic	-2.939	Highly Destabilizing	0.993	D	0.855	deleterious	D	0.542489034	None	None	N
L/I	0.0855	likely_benign	0.1168	benign	-0.791	Destabilizing	0.114	N	0.619	neutral	D	0.526312504	None	None	N
L/K	0.989	likely_pathogenic	0.9939	pathogenic	-2.169	Highly Destabilizing	0.945	D	0.842	deleterious	None	None	None	None	N
L/M	0.2203	likely_benign	0.2883	benign	-0.931	Destabilizing	0.332	N	0.535	neutral	None	None	None	None	N
L/N	0.9922	likely_pathogenic	0.9963	pathogenic	-2.833	Highly Destabilizing	0.981	D	0.881	deleterious	None	None	None	None	N
L/P	0.9942	likely_pathogenic	0.9973	pathogenic	-1.373	Destabilizing	0.975	D	0.871	deleterious	D	0.55384534	None	None	N
L/Q	0.979	likely_pathogenic	0.9888	pathogenic	-2.53	Highly Destabilizing	0.945	D	0.859	deleterious	None	None	None	None	N
L/R	0.9786	likely_pathogenic	0.9878	pathogenic	-2.153	Highly Destabilizing	0.928	D	0.852	deleterious	D	0.55384534	None	None	N
L/S	0.984	likely_pathogenic	0.9934	pathogenic	-3.402	Highly Destabilizing	0.894	D	0.835	deleterious	None	None	None	None	N
L/T	0.9257	likely_pathogenic	0.969	pathogenic	-2.93	Highly Destabilizing	0.894	D	0.759	deleterious	None	None	None	None	N
L/V	0.0932	likely_benign	0.1636	benign	-1.373	Destabilizing	0.006	N	0.373	neutral	N	0.51257072	None	None	N
L/W	0.9023	likely_pathogenic	0.9514	pathogenic	-2.132	Highly Destabilizing	0.995	D	0.827	deleterious	None	None	None	None	N
L/Y	0.8778	likely_pathogenic	0.9378	pathogenic	-1.823	Destabilizing	0.945	D	0.737	prob.delet.	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.