TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9354	28285;28286;28287	chr2:178711176;178711175;178711174	chr2:179575903;179575902;179575901
N2AB	9037	27334;27335;27336	chr2:178711176;178711175;178711174	chr2:179575903;179575902;179575901
N2A	8110	24553;24554;24555	chr2:178711176;178711175;178711174	chr2:179575903;179575902;179575901
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-79
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.3409
• 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
N/S	None	None	0.716	None	0.545	0.322	0.225902525712	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
N/A	0.3442	ambiguous	0.4617	ambiguous	-0.902	Destabilizing	0.769	D	0.675	prob.neutral	None	None	None	None	N
N/C	0.4103	ambiguous	0.5212	ambiguous	0.062	Stabilizing	0.998	D	0.785	deleterious	None	None	None	None	N
N/D	0.1612	likely_benign	0.2105	benign	-0.086	Destabilizing	0.834	D	0.575	neutral	None	None	None	None	N
N/E	0.4226	ambiguous	0.5552	ambiguous	-0.025	Destabilizing	0.769	D	0.577	neutral	None	None	None	None	N
N/F	0.6053	likely_pathogenic	0.7218	pathogenic	-0.892	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
N/G	0.2395	likely_benign	0.3196	benign	-1.197	Destabilizing	0.87	D	0.566	neutral	None	None	None	None	N
N/H	0.0926	likely_benign	0.1205	benign	-1.002	Destabilizing	0.973	D	0.733	prob.delet.	None	None	None	None	N
N/I	0.4645	ambiguous	0.5973	pathogenic	-0.172	Destabilizing	0.973	D	0.799	deleterious	None	None	None	None	N
N/K	0.1964	likely_benign	0.3198	benign	-0.055	Destabilizing	0.016	N	0.309	neutral	None	None	None	None	N
N/L	0.3654	ambiguous	0.4794	ambiguous	-0.172	Destabilizing	0.959	D	0.743	deleterious	None	None	None	None	N
N/M	0.4455	ambiguous	0.563	ambiguous	0.281	Stabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
N/P	0.8114	likely_pathogenic	0.9045	pathogenic	-0.386	Destabilizing	0.979	D	0.787	deleterious	None	None	None	None	N
N/Q	0.2667	likely_benign	0.3751	ambiguous	-0.625	Destabilizing	0.921	D	0.745	deleterious	None	None	None	None	N
N/R	0.2119	likely_benign	0.3208	benign	-0.074	Destabilizing	0.921	D	0.664	neutral	None	None	None	None	N
N/S	0.1042	likely_benign	0.1241	benign	-0.643	Destabilizing	0.716	D	0.545	neutral	None	None	None	None	N
N/T	0.2253	likely_benign	0.2924	benign	-0.384	Destabilizing	0.834	D	0.601	neutral	None	None	None	None	N
N/V	0.474	ambiguous	0.6146	pathogenic	-0.386	Destabilizing	0.959	D	0.783	deleterious	None	None	None	None	N
N/W	0.7965	likely_pathogenic	0.8996	pathogenic	-0.663	Destabilizing	0.998	D	0.768	deleterious	None	None	None	None	N
N/Y	0.1908	likely_benign	0.2642	benign	-0.457	Destabilizing	0.991	D	0.79	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.