TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25353	76282;76283;76284	chr2:178570075;178570074;178570073	chr2:179434802;179434801;179434800
N2AB	23712	71359;71360;71361	chr2:178570075;178570074;178570073	chr2:179434802;179434801;179434800
N2A	22785	68578;68579;68580	chr2:178570075;178570074;178570073	chr2:179434802;179434801;179434800
N2B	16288	49087;49088;49089	chr2:178570075;178570074;178570073	chr2:179434802;179434801;179434800
Novex-1	16413	49462;49463;49464	chr2:178570075;178570074;178570073	chr2:179434802;179434801;179434800
Novex-2	16480	49663;49664;49665	chr2:178570075;178570074;178570073	chr2:179434802;179434801;179434800
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-72
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.3731
• 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
R/G	None	None	1.0	N	0.721	0.482	0.690070301869	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
R/K	None	None	0.997	N	0.497	0.29	0.263140351381	gnomAD-4.0.0	1.5921E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43291E-05	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
R/A	0.8402	likely_pathogenic	0.8154	pathogenic	-0.336	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	I
R/C	0.5103	ambiguous	0.4716	ambiguous	-0.243	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
R/D	0.977	likely_pathogenic	0.9752	pathogenic	0.009	Stabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
R/E	0.9096	likely_pathogenic	0.9024	pathogenic	0.096	Stabilizing	0.999	D	0.652	neutral	None	None	None	None	I
R/F	0.9284	likely_pathogenic	0.9253	pathogenic	-0.387	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
R/G	0.8044	likely_pathogenic	0.775	pathogenic	-0.595	Destabilizing	1.0	D	0.721	prob.delet.	N	0.497057136	None	None	I
R/H	0.3401	ambiguous	0.3306	benign	-1.059	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
R/I	0.753	likely_pathogenic	0.7511	pathogenic	0.333	Stabilizing	1.0	D	0.784	deleterious	N	0.510323465	None	None	I
R/K	0.1687	likely_benign	0.183	benign	-0.329	Destabilizing	0.997	D	0.497	neutral	N	0.422992482	None	None	I
R/L	0.6576	likely_pathogenic	0.6308	pathogenic	0.333	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
R/M	0.8064	likely_pathogenic	0.805	pathogenic	0.026	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
R/N	0.9518	likely_pathogenic	0.9503	pathogenic	0.167	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
R/P	0.712	likely_pathogenic	0.6663	pathogenic	0.131	Stabilizing	1.0	D	0.774	deleterious	None	None	None	None	I
R/Q	0.3483	ambiguous	0.3355	benign	-0.021	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
R/S	0.923	likely_pathogenic	0.9134	pathogenic	-0.412	Destabilizing	1.0	D	0.781	deleterious	N	0.512726265	None	None	I
R/T	0.8203	likely_pathogenic	0.8134	pathogenic	-0.167	Destabilizing	1.0	D	0.771	deleterious	N	0.48615574	None	None	I
R/V	0.7729	likely_pathogenic	0.7593	pathogenic	0.131	Stabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
R/W	0.6386	likely_pathogenic	0.6064	pathogenic	-0.227	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
R/Y	0.8304	likely_pathogenic	0.8201	pathogenic	0.13	Stabilizing	1.0	D	0.785	deleterious	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.