TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34954	105085;105086;105087	chr2:178531755;178531754;178531753	chr2:179396482;179396481;179396480
N2AB	33313	100162;100163;100164	chr2:178531755;178531754;178531753	chr2:179396482;179396481;179396480
N2A	32386	97381;97382;97383	chr2:178531755;178531754;178531753	chr2:179396482;179396481;179396480
N2B	25889	77890;77891;77892	chr2:178531755;178531754;178531753	chr2:179396482;179396481;179396480
Novex-1	26014	78265;78266;78267	chr2:178531755;178531754;178531753	chr2:179396482;179396481;179396480
Novex-2	26081	78466;78467;78468	chr2:178531755;178531754;178531753	chr2:179396482;179396481;179396480
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-163
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.286
• 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
P/L	rs1689198573	None	1.0	N	0.783	0.437	0.769452518284	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
P/S	None	None	1.0	N	0.726	0.405	0.357313475932	gnomAD-4.0.0	1.59089E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85755E-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
P/A	0.1625	likely_benign	0.1891	benign	-0.743	Destabilizing	1.0	D	0.685	prob.neutral	N	0.475528606	None	None	N
P/C	0.8213	likely_pathogenic	0.8525	pathogenic	-0.574	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
P/D	0.8631	likely_pathogenic	0.8896	pathogenic	-0.668	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
P/E	0.7044	likely_pathogenic	0.7634	pathogenic	-0.789	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
P/F	0.8295	likely_pathogenic	0.8651	pathogenic	-0.96	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
P/G	0.6228	likely_pathogenic	0.6853	pathogenic	-0.897	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
P/H	0.5156	ambiguous	0.5709	pathogenic	-0.452	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
P/I	0.6942	likely_pathogenic	0.7491	pathogenic	-0.481	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
P/K	0.6968	likely_pathogenic	0.7462	pathogenic	-0.617	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
P/L	0.2982	likely_benign	0.3305	benign	-0.481	Destabilizing	1.0	D	0.783	deleterious	N	0.482051934	None	None	N
P/M	0.7042	likely_pathogenic	0.7443	pathogenic	-0.32	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
P/N	0.745	likely_pathogenic	0.7836	pathogenic	-0.277	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
P/Q	0.4127	ambiguous	0.4756	ambiguous	-0.589	Destabilizing	1.0	D	0.706	prob.neutral	N	0.445379058	None	None	N
P/R	0.423	ambiguous	0.5015	ambiguous	None	Stabilizing	1.0	D	0.779	deleterious	N	0.483340013	None	None	N
P/S	0.3076	likely_benign	0.3531	ambiguous	-0.631	Destabilizing	1.0	D	0.726	prob.delet.	N	0.460865798	None	None	N
P/T	0.3474	ambiguous	0.3928	ambiguous	-0.657	Destabilizing	1.0	D	0.715	prob.delet.	N	0.479376988	None	None	N
P/V	0.5346	ambiguous	0.5992	pathogenic	-0.533	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
P/W	0.9346	likely_pathogenic	0.9499	pathogenic	-1.019	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
P/Y	0.8179	likely_pathogenic	0.854	pathogenic	-0.733	Destabilizing	1.0	D	0.754	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.