TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30360	91303;91304;91305	chr2:178551822;178551821;178551820	chr2:179416549;179416548;179416547
N2AB	28719	86380;86381;86382	chr2:178551822;178551821;178551820	chr2:179416549;179416548;179416547
N2A	27792	83599;83600;83601	chr2:178551822;178551821;178551820	chr2:179416549;179416548;179416547
N2B	21295	64108;64109;64110	chr2:178551822;178551821;178551820	chr2:179416549;179416548;179416547
Novex-1	21420	64483;64484;64485	chr2:178551822;178551821;178551820	chr2:179416549;179416548;179416547
Novex-2	21487	64684;64685;64686	chr2:178551822;178551821;178551820	chr2:179416549;179416548;179416547
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-109
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.2579
• 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
H/R	None	None	0.879	N	0.652	0.3	0.21279746466	gnomAD-4.0.0	1.59114E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85806E-06	0	0
H/Y	rs1033418419	None	0.003	N	0.506	0.092	0.18274738541	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-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
H/A	0.5821	likely_pathogenic	0.5334	ambiguous	-1.883	Destabilizing	0.575	D	0.625	neutral	None	None	None	None	N
H/C	0.1708	likely_benign	0.1611	benign	-1.09	Destabilizing	0.991	D	0.761	deleterious	None	None	None	None	N
H/D	0.729	likely_pathogenic	0.6711	pathogenic	-1.824	Destabilizing	0.879	D	0.678	prob.neutral	N	0.472957156	None	None	N
H/E	0.681	likely_pathogenic	0.6268	pathogenic	-1.633	Destabilizing	0.733	D	0.633	neutral	None	None	None	None	N
H/F	0.1913	likely_benign	0.1821	benign	0.101	Stabilizing	0.704	D	0.671	neutral	None	None	None	None	N
H/G	0.7666	likely_pathogenic	0.7326	pathogenic	-2.277	Highly Destabilizing	0.733	D	0.659	neutral	None	None	None	None	N
H/I	0.2538	likely_benign	0.2241	benign	-0.707	Destabilizing	0.826	D	0.771	deleterious	None	None	None	None	N
H/K	0.5916	likely_pathogenic	0.5323	ambiguous	-1.402	Destabilizing	0.826	D	0.675	neutral	None	None	None	None	N
H/L	0.1734	likely_benign	0.151	benign	-0.707	Destabilizing	0.338	N	0.701	prob.neutral	N	0.464607031	None	None	N
H/M	0.4988	ambiguous	0.4546	ambiguous	-0.907	Destabilizing	0.991	D	0.739	prob.delet.	None	None	None	None	N
H/N	0.2375	likely_benign	0.2056	benign	-1.954	Destabilizing	0.674	D	0.642	neutral	N	0.486617099	None	None	N
H/P	0.9285	likely_pathogenic	0.9238	pathogenic	-1.091	Destabilizing	0.957	D	0.745	deleterious	N	0.490611902	None	None	N
H/Q	0.3634	ambiguous	0.3197	benign	-1.512	Destabilizing	0.879	D	0.663	neutral	N	0.482307358	None	None	N
H/R	0.2434	likely_benign	0.2169	benign	-1.686	Destabilizing	0.879	D	0.652	neutral	N	0.475437314	None	None	N
H/S	0.4332	ambiguous	0.389	ambiguous	-2.066	Highly Destabilizing	0.575	D	0.657	neutral	None	None	None	None	N
H/T	0.4125	ambiguous	0.3815	ambiguous	-1.769	Destabilizing	0.906	D	0.677	prob.neutral	None	None	None	None	N
H/V	0.2659	likely_benign	0.2393	benign	-1.091	Destabilizing	0.826	D	0.723	prob.delet.	None	None	None	None	N
H/W	0.2636	likely_benign	0.2631	benign	0.587	Stabilizing	0.973	D	0.737	prob.delet.	None	None	None	None	N
H/Y	0.0798	likely_benign	0.0766	benign	0.359	Stabilizing	0.003	N	0.506	neutral	N	0.450120369	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.