TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32813	98662;98663;98664	chr2:178539628;178539627;178539626	chr2:179404355;179404354;179404353
N2AB	31172	93739;93740;93741	chr2:178539628;178539627;178539626	chr2:179404355;179404354;179404353
N2A	30245	90958;90959;90960	chr2:178539628;178539627;178539626	chr2:179404355;179404354;179404353
N2B	23748	71467;71468;71469	chr2:178539628;178539627;178539626	chr2:179404355;179404354;179404353
Novex-1	23873	71842;71843;71844	chr2:178539628;178539627;178539626	chr2:179404355;179404354;179404353
Novex-2	23940	72043;72044;72045	chr2:178539628;178539627;178539626	chr2:179404355;179404354;179404353
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-127
• Domain position: 19
• Structural Position: 20
• Q(SASA): 0.0949
• 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/L	None	None	0.948	N	0.382	0.186	0.336892272479	gnomAD-4.0.0	6.84202E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99454E-07	0	0
V/M	rs1693400485	None	0.948	N	0.45	0.198	0.369867359543	gnomAD-4.0.0	2.05261E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69836E-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	0.617	likely_pathogenic	0.5614	ambiguous	-2.651	Highly Destabilizing	0.989	D	0.625	neutral	N	0.497153806	None	None	N
V/C	0.8785	likely_pathogenic	0.8585	pathogenic	-2.143	Highly Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
V/D	0.9971	likely_pathogenic	0.9959	pathogenic	-3.471	Highly Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
V/E	0.9882	likely_pathogenic	0.9853	pathogenic	-3.156	Highly Destabilizing	0.999	D	0.799	deleterious	N	0.515710234	None	None	N
V/F	0.77	likely_pathogenic	0.7197	pathogenic	-1.474	Destabilizing	0.998	D	0.788	deleterious	None	None	None	None	N
V/G	0.8532	likely_pathogenic	0.8242	pathogenic	-3.243	Highly Destabilizing	0.998	D	0.819	deleterious	N	0.504353928	None	None	N
V/H	0.9959	likely_pathogenic	0.9938	pathogenic	-3.041	Highly Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
V/I	0.1156	likely_benign	0.1056	benign	-0.919	Destabilizing	0.611	D	0.278	neutral	None	None	None	None	N
V/K	0.9891	likely_pathogenic	0.9864	pathogenic	-2.083	Highly Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
V/L	0.41	ambiguous	0.3654	ambiguous	-0.919	Destabilizing	0.948	D	0.382	neutral	N	0.474738306	None	None	N
V/M	0.5173	ambiguous	0.4305	ambiguous	-1.278	Destabilizing	0.948	D	0.45	neutral	N	0.472644938	None	None	N
V/N	0.9883	likely_pathogenic	0.9829	pathogenic	-2.748	Highly Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
V/P	0.9961	likely_pathogenic	0.9945	pathogenic	-1.479	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
V/Q	0.9789	likely_pathogenic	0.9739	pathogenic	-2.387	Highly Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
V/R	0.9761	likely_pathogenic	0.9717	pathogenic	-2.137	Highly Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
V/S	0.9248	likely_pathogenic	0.8962	pathogenic	-3.261	Highly Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
V/T	0.8155	likely_pathogenic	0.7678	pathogenic	-2.792	Highly Destabilizing	0.996	D	0.674	neutral	None	None	None	None	N
V/W	0.9963	likely_pathogenic	0.9948	pathogenic	-1.999	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
V/Y	0.9809	likely_pathogenic	0.975	pathogenic	-1.753	Destabilizing	1.0	D	0.762	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.