TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33073	99442;99443;99444	chr2:178538612;178538611;178538610	chr2:179403339;179403338;179403337
N2AB	31432	94519;94520;94521	chr2:178538612;178538611;178538610	chr2:179403339;179403338;179403337
N2A	30505	91738;91739;91740	chr2:178538612;178538611;178538610	chr2:179403339;179403338;179403337
N2B	24008	72247;72248;72249	chr2:178538612;178538611;178538610	chr2:179403339;179403338;179403337
Novex-1	24133	72622;72623;72624	chr2:178538612;178538611;178538610	chr2:179403339;179403338;179403337
Novex-2	24200	72823;72824;72825	chr2:178538612;178538611;178538610	chr2:179403339;179403338;179403337
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: Fn3-129
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0776
• 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/A	None	None	0.994	D	0.589	0.781	0.771421751781	gnomAD-4.0.0	3.18287E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71723E-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	0.7773	likely_pathogenic	0.804	pathogenic	-2.566	Highly Destabilizing	0.994	D	0.589	neutral	D	0.561860737	None	None	N
V/C	0.9393	likely_pathogenic	0.9398	pathogenic	-1.891	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
V/D	0.9978	likely_pathogenic	0.9978	pathogenic	-3.532	Highly Destabilizing	0.999	D	0.889	deleterious	D	0.646896015	None	None	N
V/E	0.9939	likely_pathogenic	0.9944	pathogenic	-3.235	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/F	0.8532	likely_pathogenic	0.8581	pathogenic	-1.587	Destabilizing	0.998	D	0.802	deleterious	D	0.579964992	None	None	N
V/G	0.912	likely_pathogenic	0.9153	pathogenic	-3.098	Highly Destabilizing	0.999	D	0.884	deleterious	D	0.646896015	None	None	N
V/H	0.9978	likely_pathogenic	0.9981	pathogenic	-2.909	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/I	0.1008	likely_benign	0.0953	benign	-0.99	Destabilizing	0.543	D	0.288	neutral	N	0.505107726	None	None	N
V/K	0.9964	likely_pathogenic	0.9969	pathogenic	-2.225	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
V/L	0.5115	ambiguous	0.5248	ambiguous	-0.99	Destabilizing	0.948	D	0.512	neutral	N	0.517317207	None	None	N
V/M	0.6842	likely_pathogenic	0.7091	pathogenic	-1.197	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
V/N	0.9897	likely_pathogenic	0.9907	pathogenic	-2.903	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
V/P	0.9914	likely_pathogenic	0.9954	pathogenic	-1.503	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/Q	0.9925	likely_pathogenic	0.9936	pathogenic	-2.586	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
V/R	0.9919	likely_pathogenic	0.9925	pathogenic	-2.224	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
V/S	0.95	likely_pathogenic	0.9529	pathogenic	-3.318	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/T	0.8878	likely_pathogenic	0.8943	pathogenic	-2.886	Highly Destabilizing	0.996	D	0.661	neutral	None	None	None	None	N
V/W	0.9981	likely_pathogenic	0.9982	pathogenic	-2.078	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
V/Y	0.9872	likely_pathogenic	0.9882	pathogenic	-1.847	Destabilizing	1.0	D	0.803	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.