TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19342	58249;58250;58251	chr2:178594470;178594469;178594468	chr2:179459197;179459196;179459195
N2AB	17701	53326;53327;53328	chr2:178594470;178594469;178594468	chr2:179459197;179459196;179459195
N2A	16774	50545;50546;50547	chr2:178594470;178594469;178594468	chr2:179459197;179459196;179459195
N2B	10277	31054;31055;31056	chr2:178594470;178594469;178594468	chr2:179459197;179459196;179459195
Novex-1	10402	31429;31430;31431	chr2:178594470;178594469;178594468	chr2:179459197;179459196;179459195
Novex-2	10469	31630;31631;31632	chr2:178594470;178594469;178594468	chr2:179459197;179459196;179459195
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-28
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.3195
• 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
R/I	None	None	0.998	N	0.71	0.34	0.596289430357	gnomAD-4.0.0	2.05311E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69887E-06	0	0
R/K	None	None	0.973	N	0.555	0.26	0.201204373187	gnomAD-4.0.0	6.84371E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99622E-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
R/A	0.7878	likely_pathogenic	0.8146	pathogenic	-1.076	Destabilizing	0.96	D	0.578	neutral	None	None	None	None	N
R/C	0.2924	likely_benign	0.3247	benign	-1.045	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
R/D	0.8894	likely_pathogenic	0.904	pathogenic	-0.532	Destabilizing	0.998	D	0.635	neutral	None	None	None	None	N
R/E	0.6495	likely_pathogenic	0.6693	pathogenic	-0.332	Destabilizing	0.992	D	0.527	neutral	None	None	None	None	N
R/F	0.9248	likely_pathogenic	0.9355	pathogenic	-0.537	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
R/G	0.5589	ambiguous	0.5942	pathogenic	-1.432	Destabilizing	0.989	D	0.587	neutral	N	0.470124109	None	None	N
R/H	0.3081	likely_benign	0.3158	benign	-1.637	Destabilizing	1.0	D	0.582	neutral	None	None	None	None	N
R/I	0.7893	likely_pathogenic	0.8175	pathogenic	-0.082	Destabilizing	0.998	D	0.71	prob.delet.	N	0.466236542	None	None	N
R/K	0.1788	likely_benign	0.2126	benign	-0.737	Destabilizing	0.973	D	0.555	neutral	N	0.492753638	None	None	N
R/L	0.542	ambiguous	0.5815	pathogenic	-0.082	Destabilizing	0.996	D	0.588	neutral	None	None	None	None	N
R/M	0.6626	likely_pathogenic	0.7148	pathogenic	-0.642	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
R/N	0.7964	likely_pathogenic	0.8262	pathogenic	-0.787	Destabilizing	0.992	D	0.52	neutral	None	None	None	None	N
R/P	0.7051	likely_pathogenic	0.7341	pathogenic	-0.396	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
R/Q	0.1923	likely_benign	0.1988	benign	-0.699	Destabilizing	0.999	D	0.546	neutral	None	None	None	None	N
R/S	0.824	likely_pathogenic	0.8399	pathogenic	-1.455	Destabilizing	0.775	D	0.467	neutral	N	0.508664453	None	None	N
R/T	0.4733	ambiguous	0.5114	ambiguous	-1.037	Destabilizing	0.989	D	0.565	neutral	N	0.393354648	None	None	N
R/V	0.7637	likely_pathogenic	0.7932	pathogenic	-0.396	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
R/W	0.5941	likely_pathogenic	0.5891	pathogenic	-0.214	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
R/Y	0.7831	likely_pathogenic	0.8086	pathogenic	-0.011	Destabilizing	1.0	D	0.686	prob.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.