TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31585	94978;94979;94980	chr2:178546675;178546674;178546673	chr2:179411402;179411401;179411400
N2AB	29944	90055;90056;90057	chr2:178546675;178546674;178546673	chr2:179411402;179411401;179411400
N2A	29017	87274;87275;87276	chr2:178546675;178546674;178546673	chr2:179411402;179411401;179411400
N2B	22520	67783;67784;67785	chr2:178546675;178546674;178546673	chr2:179411402;179411401;179411400
Novex-1	22645	68158;68159;68160	chr2:178546675;178546674;178546673	chr2:179411402;179411401;179411400
Novex-2	22712	68359;68360;68361	chr2:178546675;178546674;178546673	chr2:179411402;179411401;179411400
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Fn3-118
• Domain position: 80
• Structural Position: 109
• Q(SASA): 0.1797
• 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	None	None	0.994	N	0.723	0.474	0.756187549339	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.5178	ambiguous	0.3892	ambiguous	-2.758	Highly Destabilizing	0.97	D	0.716	prob.delet.	None	None	None	None	N
L/C	0.6053	likely_pathogenic	0.5533	ambiguous	-2.143	Highly Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
L/D	0.9733	likely_pathogenic	0.9511	pathogenic	-3.01	Highly Destabilizing	0.999	D	0.794	deleterious	None	None	None	None	N
L/E	0.8107	likely_pathogenic	0.6974	pathogenic	-2.854	Highly Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
L/F	0.1478	likely_benign	0.1317	benign	-1.686	Destabilizing	0.989	D	0.645	neutral	N	0.390746778	None	None	N
L/G	0.8786	likely_pathogenic	0.8165	pathogenic	-3.219	Highly Destabilizing	0.996	D	0.759	deleterious	None	None	None	None	N
L/H	0.4394	ambiguous	0.3504	ambiguous	-2.388	Highly Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
L/I	0.1113	likely_benign	0.0898	benign	-1.444	Destabilizing	0.122	N	0.393	neutral	N	0.348206722	None	None	N
L/K	0.573	likely_pathogenic	0.4503	ambiguous	-2.079	Highly Destabilizing	0.996	D	0.728	prob.delet.	None	None	None	None	N
L/M	0.1134	likely_benign	0.1	benign	-1.466	Destabilizing	0.871	D	0.529	neutral	None	None	None	None	N
L/N	0.7741	likely_pathogenic	0.6773	pathogenic	-2.271	Highly Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
L/P	0.9949	likely_pathogenic	0.9902	pathogenic	-1.863	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
L/Q	0.3163	likely_benign	0.2349	benign	-2.282	Highly Destabilizing	0.996	D	0.763	deleterious	None	None	None	None	N
L/R	0.4307	ambiguous	0.3338	benign	-1.572	Destabilizing	0.996	D	0.766	deleterious	None	None	None	None	N
L/S	0.5564	ambiguous	0.4336	ambiguous	-2.948	Highly Destabilizing	0.994	D	0.723	prob.delet.	N	0.416893229	None	None	N
L/T	0.3471	ambiguous	0.2393	benign	-2.667	Highly Destabilizing	0.97	D	0.701	prob.neutral	None	None	None	None	N
L/V	0.1268	likely_benign	0.0992	benign	-1.863	Destabilizing	0.248	N	0.455	neutral	N	0.402905212	None	None	N
L/W	0.3822	ambiguous	0.3652	ambiguous	-1.931	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
L/Y	0.4443	ambiguous	0.4132	ambiguous	-1.743	Destabilizing	0.999	D	0.747	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.