TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21887	65884;65885;65886	chr2:178583144;178583143;178583142	chr2:179447871;179447870;179447869
N2AB	20246	60961;60962;60963	chr2:178583144;178583143;178583142	chr2:179447871;179447870;179447869
N2A	19319	58180;58181;58182	chr2:178583144;178583143;178583142	chr2:179447871;179447870;179447869
N2B	12822	38689;38690;38691	chr2:178583144;178583143;178583142	chr2:179447871;179447870;179447869
Novex-1	12947	39064;39065;39066	chr2:178583144;178583143;178583142	chr2:179447871;179447870;179447869
Novex-2	13014	39265;39266;39267	chr2:178583144;178583143;178583142	chr2:179447871;179447870;179447869
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-125
• Domain position: 22
• Structural Position: 35
• Q(SASA): 0.1563
• 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
V/I	None	None	0.767	N	0.25	0.244	0.556581311739	gnomAD-4.0.0	3.18865E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72659E-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
V/A	0.8123	likely_pathogenic	0.7654	pathogenic	-1.542	Destabilizing	0.998	D	0.594	neutral	N	0.486546181	None	None	N
V/C	0.9582	likely_pathogenic	0.9455	pathogenic	-0.717	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
V/D	0.9972	likely_pathogenic	0.9963	pathogenic	-1.406	Destabilizing	1.0	D	0.851	deleterious	D	0.60364195	None	None	N
V/E	0.9914	likely_pathogenic	0.9898	pathogenic	-1.406	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
V/F	0.7385	likely_pathogenic	0.6541	pathogenic	-1.259	Destabilizing	0.999	D	0.829	deleterious	D	0.533185338	None	None	N
V/G	0.942	likely_pathogenic	0.9235	pathogenic	-1.865	Destabilizing	1.0	D	0.85	deleterious	D	0.571371064	None	None	N
V/H	0.9957	likely_pathogenic	0.9941	pathogenic	-1.484	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
V/I	0.0978	likely_benign	0.0937	benign	-0.746	Destabilizing	0.767	D	0.25	neutral	N	0.505129155	None	None	N
V/K	0.9933	likely_pathogenic	0.9917	pathogenic	-1.197	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
V/L	0.6045	likely_pathogenic	0.5321	ambiguous	-0.746	Destabilizing	0.981	D	0.61	neutral	D	0.57612662	None	None	N
V/M	0.6435	likely_pathogenic	0.5747	pathogenic	-0.419	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
V/N	0.9903	likely_pathogenic	0.9869	pathogenic	-0.884	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/P	0.9882	likely_pathogenic	0.9861	pathogenic	-0.978	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
V/Q	0.9889	likely_pathogenic	0.9862	pathogenic	-1.056	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/R	0.9852	likely_pathogenic	0.9822	pathogenic	-0.692	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/S	0.9519	likely_pathogenic	0.9352	pathogenic	-1.362	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
V/T	0.8879	likely_pathogenic	0.8608	pathogenic	-1.257	Destabilizing	0.998	D	0.677	prob.neutral	None	None	None	None	N
V/W	0.995	likely_pathogenic	0.9925	pathogenic	-1.482	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
V/Y	0.9711	likely_pathogenic	0.9593	pathogenic	-1.195	Destabilizing	1.0	D	0.826	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.