TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21838	65737;65738;65739	chr2:178583670;178583669;178583668	chr2:179448397;179448396;179448395
N2AB	20197	60814;60815;60816	chr2:178583670;178583669;178583668	chr2:179448397;179448396;179448395
N2A	19270	58033;58034;58035	chr2:178583670;178583669;178583668	chr2:179448397;179448396;179448395
N2B	12773	38542;38543;38544	chr2:178583670;178583669;178583668	chr2:179448397;179448396;179448395
Novex-1	12898	38917;38918;38919	chr2:178583670;178583669;178583668	chr2:179448397;179448396;179448395
Novex-2	12965	39118;39119;39120	chr2:178583670;178583669;178583668	chr2:179448397;179448396;179448395
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-46
• Domain position: 82
• Structural Position: 112
• Q(SASA): 0.0962
• 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
T/N	rs1458673199	-1.385	1.0	N	0.827	0.379	0.31411915649	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.67448E-04
T/N	rs1458673199	-1.385	1.0	N	0.827	0.379	0.31411915649	gnomAD-4.0.0	1.595E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.03232E-05

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
T/A	0.6945	likely_pathogenic	0.5939	pathogenic	-1.026	Destabilizing	0.999	D	0.617	neutral	N	0.46772148	None	None	N
T/C	0.8634	likely_pathogenic	0.8066	pathogenic	-0.996	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
T/D	0.9175	likely_pathogenic	0.888	pathogenic	-1.555	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
T/E	0.9694	likely_pathogenic	0.9612	pathogenic	-1.464	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
T/F	0.9826	likely_pathogenic	0.9693	pathogenic	-0.892	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
T/G	0.8032	likely_pathogenic	0.7343	pathogenic	-1.342	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
T/H	0.9111	likely_pathogenic	0.8803	pathogenic	-1.516	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
T/I	0.968	likely_pathogenic	0.9503	pathogenic	-0.245	Destabilizing	1.0	D	0.847	deleterious	N	0.468481949	None	None	N
T/K	0.956	likely_pathogenic	0.9429	pathogenic	-0.875	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
T/L	0.7878	likely_pathogenic	0.7145	pathogenic	-0.245	Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
T/M	0.6617	likely_pathogenic	0.5616	ambiguous	-0.079	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
T/N	0.2248	likely_benign	0.2028	benign	-1.235	Destabilizing	1.0	D	0.827	deleterious	N	0.326588151	None	None	N
T/P	0.8896	likely_pathogenic	0.8514	pathogenic	-0.475	Destabilizing	1.0	D	0.854	deleterious	N	0.46797497	None	None	N
T/Q	0.9471	likely_pathogenic	0.9287	pathogenic	-1.339	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
T/R	0.9473	likely_pathogenic	0.9309	pathogenic	-0.717	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
T/S	0.4026	ambiguous	0.3051	benign	-1.406	Destabilizing	0.999	D	0.632	neutral	N	0.477112182	None	None	N
T/V	0.8834	likely_pathogenic	0.8467	pathogenic	-0.475	Destabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	N
T/W	0.9942	likely_pathogenic	0.9908	pathogenic	-0.92	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
T/Y	0.9715	likely_pathogenic	0.953	pathogenic	-0.606	Destabilizing	1.0	D	0.856	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.