TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24437	73534;73535;73536	chr2:178572823;178572822;178572821	chr2:179437550;179437549;179437548
N2AB	22796	68611;68612;68613	chr2:178572823;178572822;178572821	chr2:179437550;179437549;179437548
N2A	21869	65830;65831;65832	chr2:178572823;178572822;178572821	chr2:179437550;179437549;179437548
N2B	15372	46339;46340;46341	chr2:178572823;178572822;178572821	chr2:179437550;179437549;179437548
Novex-1	15497	46714;46715;46716	chr2:178572823;178572822;178572821	chr2:179437550;179437549;179437548
Novex-2	15564	46915;46916;46917	chr2:178572823;178572822;178572821	chr2:179437550;179437549;179437548
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-132
• Domain position: 7
• Structural Position: 11
• Q(SASA): 0.2704
• Predicted PPI site: I

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/A	None	None	0.999	N	0.6	0.16	0.544738774389	gnomAD-4.0.0	6.84341E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15955E-05	0
V/D	None	None	1.0	N	0.747	0.401	0.818452415539	gnomAD-4.0.0	1.36868E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79921E-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	0.1761	likely_benign	0.2303	benign	-0.827	Destabilizing	0.999	D	0.6	neutral	N	0.461692517	None	None	I
V/C	0.7355	likely_pathogenic	0.801	pathogenic	-0.749	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
V/D	0.6762	likely_pathogenic	0.7315	pathogenic	-0.266	Destabilizing	1.0	D	0.747	deleterious	N	0.480048992	None	None	I
V/E	0.5731	likely_pathogenic	0.6134	pathogenic	-0.357	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	I
V/F	0.2342	likely_benign	0.305	benign	-0.875	Destabilizing	1.0	D	0.723	prob.delet.	N	0.513102773	None	None	I
V/G	0.2478	likely_benign	0.2911	benign	-1.009	Destabilizing	1.0	D	0.711	prob.delet.	N	0.455806695	None	None	I
V/H	0.7412	likely_pathogenic	0.8013	pathogenic	-0.532	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	I
V/I	0.0747	likely_benign	0.0862	benign	-0.482	Destabilizing	0.997	D	0.547	neutral	N	0.462865953	None	None	I
V/K	0.7138	likely_pathogenic	0.7478	pathogenic	-0.606	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
V/L	0.1818	likely_benign	0.2992	benign	-0.482	Destabilizing	0.997	D	0.59	neutral	N	0.519623313	None	None	I
V/M	0.1172	likely_benign	0.1722	benign	-0.422	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	I
V/N	0.3266	likely_benign	0.3918	ambiguous	-0.337	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
V/P	0.7077	likely_pathogenic	0.7418	pathogenic	-0.561	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
V/Q	0.5128	ambiguous	0.579	pathogenic	-0.579	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
V/R	0.6858	likely_pathogenic	0.7224	pathogenic	-0.096	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	I
V/S	0.2444	likely_benign	0.3064	benign	-0.804	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
V/T	0.1474	likely_benign	0.1786	benign	-0.79	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	I
V/W	0.8399	likely_pathogenic	0.8996	pathogenic	-0.93	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
V/Y	0.6331	likely_pathogenic	0.7121	pathogenic	-0.643	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I

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.