TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21646	65161;65162;65163	chr2:178584705;178584704;178584703	chr2:179449432;179449431;179449430
N2AB	20005	60238;60239;60240	chr2:178584705;178584704;178584703	chr2:179449432;179449431;179449430
N2A	19078	57457;57458;57459	chr2:178584705;178584704;178584703	chr2:179449432;179449431;179449430
N2B	12581	37966;37967;37968	chr2:178584705;178584704;178584703	chr2:179449432;179449431;179449430
Novex-1	12706	38341;38342;38343	chr2:178584705;178584704;178584703	chr2:179449432;179449431;179449430
Novex-2	12773	38542;38543;38544	chr2:178584705;178584704;178584703	chr2:179449432;179449431;179449430
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-44
• Domain position: 88
• Structural Position: 121
• Q(SASA): 0.117
• 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	rs1203566511	None	0.933	N	0.609	0.321	0.591436515814	gnomAD-4.0.0	1.59196E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85976E-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	0.3979	ambiguous	0.3795	ambiguous	-2.529	Highly Destabilizing	0.841	D	0.587	neutral	None	None	None	None	N
L/C	0.6017	likely_pathogenic	0.5886	pathogenic	-1.65	Destabilizing	0.998	D	0.664	prob.neutral	None	None	None	None	N
L/D	0.9448	likely_pathogenic	0.9523	pathogenic	-3.142	Highly Destabilizing	0.991	D	0.839	deleterious	None	None	None	None	N
L/E	0.6909	likely_pathogenic	0.7109	pathogenic	-2.917	Highly Destabilizing	0.991	D	0.827	deleterious	None	None	None	None	N
L/F	0.4245	ambiguous	0.4293	ambiguous	-1.55	Destabilizing	0.933	D	0.609	neutral	N	0.518369348	None	None	N
L/G	0.8072	likely_pathogenic	0.8135	pathogenic	-3.044	Highly Destabilizing	0.991	D	0.773	deleterious	None	None	None	None	N
L/H	0.6191	likely_pathogenic	0.6413	pathogenic	-2.638	Highly Destabilizing	0.997	D	0.864	deleterious	D	0.531157685	None	None	N
L/I	0.1095	likely_benign	0.1063	benign	-1.032	Destabilizing	0.005	N	0.255	neutral	N	0.503235282	None	None	N
L/K	0.6048	likely_pathogenic	0.6335	pathogenic	-2.081	Highly Destabilizing	0.974	D	0.641	neutral	None	None	None	None	N
L/M	0.158	likely_benign	0.1553	benign	-0.909	Destabilizing	0.949	D	0.621	neutral	None	None	None	None	N
L/N	0.7451	likely_pathogenic	0.7597	pathogenic	-2.443	Highly Destabilizing	0.991	D	0.843	deleterious	None	None	None	None	N
L/P	0.9766	likely_pathogenic	0.9839	pathogenic	-1.514	Destabilizing	0.989	D	0.831	deleterious	N	0.489113051	None	None	N
L/Q	0.3472	ambiguous	0.3594	ambiguous	-2.302	Highly Destabilizing	0.991	D	0.741	deleterious	None	None	None	None	N
L/R	0.5217	ambiguous	0.5484	ambiguous	-1.768	Destabilizing	0.989	D	0.705	prob.delet.	N	0.51305343	None	None	N
L/S	0.5571	ambiguous	0.5449	ambiguous	-3.025	Highly Destabilizing	0.974	D	0.566	neutral	None	None	None	None	N
L/T	0.3512	ambiguous	0.3299	benign	-2.673	Highly Destabilizing	0.841	D	0.626	neutral	None	None	None	None	N
L/V	0.1114	likely_benign	0.1108	benign	-1.514	Destabilizing	0.051	N	0.278	neutral	D	0.529957737	None	None	N
L/W	0.7655	likely_pathogenic	0.7866	pathogenic	-2.054	Highly Destabilizing	0.998	D	0.786	deleterious	None	None	None	None	N
L/Y	0.7045	likely_pathogenic	0.7227	pathogenic	-1.736	Destabilizing	0.991	D	0.629	neutral	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.