TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16923	50992;50993;50994	chr2:178611462;178611461;178611460	chr2:179476189;179476188;179476187
N2AB	15282	46069;46070;46071	chr2:178611462;178611461;178611460	chr2:179476189;179476188;179476187
N2A	14355	43288;43289;43290	chr2:178611462;178611461;178611460	chr2:179476189;179476188;179476187
N2B	7858	23797;23798;23799	chr2:178611462;178611461;178611460	chr2:179476189;179476188;179476187
Novex-1	7983	24172;24173;24174	chr2:178611462;178611461;178611460	chr2:179476189;179476188;179476187
Novex-2	8050	24373;24374;24375	chr2:178611462;178611461;178611460	chr2:179476189;179476188;179476187
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-11
• Domain position: 72
• Structural Position: 103
• Q(SASA): 0.2291
• 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
E/A	None	None	0.999	N	0.696	0.49	0.424073947737	gnomAD-4.0.0	1.593E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8613E-06	0	0
E/K	None	None	0.999	N	0.612	0.291	0.32082282376	gnomAD-4.0.0	6.84537E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99774E-07	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
E/A	0.1686	likely_benign	0.2043	benign	-0.741	Destabilizing	0.999	D	0.696	prob.neutral	N	0.480601464	None	None	N
E/C	0.8929	likely_pathogenic	0.9445	pathogenic	-0.384	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
E/D	0.3414	ambiguous	0.3349	benign	-1.036	Destabilizing	0.999	D	0.488	neutral	N	0.478813222	None	None	N
E/F	0.9126	likely_pathogenic	0.9393	pathogenic	0.042	Stabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
E/G	0.2731	likely_benign	0.3201	benign	-1.153	Destabilizing	1.0	D	0.75	deleterious	D	0.535302845	None	None	N
E/H	0.7324	likely_pathogenic	0.779	pathogenic	-0.2	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
E/I	0.5573	ambiguous	0.6266	pathogenic	0.397	Stabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
E/K	0.3118	likely_benign	0.3372	benign	-0.504	Destabilizing	0.999	D	0.612	neutral	N	0.462781177	None	None	N
E/L	0.6353	likely_pathogenic	0.6905	pathogenic	0.397	Stabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/M	0.5948	likely_pathogenic	0.6687	pathogenic	0.809	Stabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
E/N	0.4439	ambiguous	0.485	ambiguous	-1.114	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
E/P	0.4836	ambiguous	0.609	pathogenic	0.039	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/Q	0.1842	likely_benign	0.2197	benign	-0.923	Destabilizing	1.0	D	0.643	neutral	N	0.484201495	None	None	N
E/R	0.4911	ambiguous	0.5586	ambiguous	-0.215	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
E/S	0.3016	likely_benign	0.3577	ambiguous	-1.468	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	N
E/T	0.3202	likely_benign	0.3656	ambiguous	-1.113	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/V	0.3436	ambiguous	0.3825	ambiguous	0.039	Stabilizing	1.0	D	0.798	deleterious	N	0.478232042	None	None	N
E/W	0.9707	likely_pathogenic	0.9814	pathogenic	0.322	Stabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
E/Y	0.8423	likely_pathogenic	0.8822	pathogenic	0.323	Stabilizing	1.0	D	0.788	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.