TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31845	95758;95759;95760	chr2:178545577;178545576;178545575	chr2:179410304;179410303;179410302
N2AB	30204	90835;90836;90837	chr2:178545577;178545576;178545575	chr2:179410304;179410303;179410302
N2A	29277	88054;88055;88056	chr2:178545577;178545576;178545575	chr2:179410304;179410303;179410302
N2B	22780	68563;68564;68565	chr2:178545577;178545576;178545575	chr2:179410304;179410303;179410302
Novex-1	22905	68938;68939;68940	chr2:178545577;178545576;178545575	chr2:179410304;179410303;179410302
Novex-2	22972	69139;69140;69141	chr2:178545577;178545576;178545575	chr2:179410304;179410303;179410302
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-120
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1126
• 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
D/N	rs772648821	-2.372	0.999	N	0.781	0.325	0.442261297928	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.56E-05	None	0	None	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
D/A	0.8359	likely_pathogenic	0.8335	pathogenic	-1.646	Destabilizing	0.999	D	0.797	deleterious	N	0.501933269	None	None	N
D/C	0.9439	likely_pathogenic	0.9499	pathogenic	-0.826	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
D/E	0.3629	ambiguous	0.3936	ambiguous	-0.822	Destabilizing	0.767	D	0.418	neutral	N	0.297199112	None	None	N
D/F	0.926	likely_pathogenic	0.9398	pathogenic	-1.46	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
D/G	0.9051	likely_pathogenic	0.9012	pathogenic	-2.025	Highly Destabilizing	0.998	D	0.77	deleterious	N	0.503146777	None	None	N
D/H	0.8318	likely_pathogenic	0.8425	pathogenic	-1.345	Destabilizing	1.0	D	0.829	deleterious	N	0.496431448	None	None	N
D/I	0.9244	likely_pathogenic	0.9377	pathogenic	-0.58	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
D/K	0.9638	likely_pathogenic	0.9693	pathogenic	-1.49	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
D/L	0.9074	likely_pathogenic	0.9167	pathogenic	-0.58	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
D/M	0.9634	likely_pathogenic	0.9689	pathogenic	0.164	Stabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
D/N	0.6146	likely_pathogenic	0.6569	pathogenic	-1.601	Destabilizing	0.999	D	0.781	deleterious	N	0.496778165	None	None	N
D/P	0.9991	likely_pathogenic	0.9991	pathogenic	-0.918	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
D/Q	0.8661	likely_pathogenic	0.8775	pathogenic	-1.329	Destabilizing	0.999	D	0.806	deleterious	None	None	None	None	N
D/R	0.9632	likely_pathogenic	0.9661	pathogenic	-1.349	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
D/S	0.6883	likely_pathogenic	0.7062	pathogenic	-2.302	Highly Destabilizing	0.997	D	0.702	prob.neutral	None	None	None	None	N
D/T	0.8843	likely_pathogenic	0.9036	pathogenic	-1.94	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
D/V	0.8375	likely_pathogenic	0.8503	pathogenic	-0.918	Destabilizing	0.999	D	0.863	deleterious	N	0.521039104	None	None	N
D/W	0.9807	likely_pathogenic	0.9832	pathogenic	-1.506	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
D/Y	0.7079	likely_pathogenic	0.7328	pathogenic	-1.271	Destabilizing	1.0	D	0.861	deleterious	N	0.46741805	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.