TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15813	47662;47663;47664	chr2:178617914;178617913;178617912	chr2:179482641;179482640;179482639
N2AB	14172	42739;42740;42741	chr2:178617914;178617913;178617912	chr2:179482641;179482640;179482639
N2A	13245	39958;39959;39960	chr2:178617914;178617913;178617912	chr2:179482641;179482640;179482639
N2B	6748	20467;20468;20469	chr2:178617914;178617913;178617912	chr2:179482641;179482640;179482639
Novex-1	6873	20842;20843;20844	chr2:178617914;178617913;178617912	chr2:179482641;179482640;179482639
Novex-2	6940	21043;21044;21045	chr2:178617914;178617913;178617912	chr2:179482641;179482640;179482639
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-2
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.1018
• 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
A/P	None	None	0.117	N	0.349	0.179	0.18995819373	gnomAD-4.0.0	1.59339E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86287E-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
A/C	0.54	ambiguous	0.4691	ambiguous	-0.811	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
A/D	0.4128	ambiguous	0.3949	ambiguous	-1.134	Destabilizing	0.997	D	0.736	prob.delet.	N	0.476792327	None	None	N
A/E	0.3034	likely_benign	0.303	benign	-1.154	Destabilizing	0.995	D	0.708	prob.delet.	None	None	None	None	N
A/F	0.6036	likely_pathogenic	0.5585	ambiguous	-0.942	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
A/G	0.1291	likely_benign	0.1152	benign	-1.119	Destabilizing	0.989	D	0.48	neutral	N	0.436682424	None	None	N
A/H	0.5868	likely_pathogenic	0.556	ambiguous	-1.291	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
A/I	0.4236	ambiguous	0.3752	ambiguous	-0.278	Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
A/K	0.4166	ambiguous	0.4062	ambiguous	-1.179	Destabilizing	0.995	D	0.705	prob.neutral	None	None	None	None	N
A/L	0.3458	ambiguous	0.3129	benign	-0.278	Destabilizing	0.991	D	0.67	neutral	None	None	None	None	N
A/M	0.3884	ambiguous	0.3437	ambiguous	-0.207	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
A/N	0.3686	ambiguous	0.3232	benign	-0.924	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
A/P	0.1229	likely_benign	0.1195	benign	-0.428	Destabilizing	0.117	N	0.349	neutral	N	0.410904068	None	None	N
A/Q	0.388	ambiguous	0.3695	ambiguous	-1.06	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
A/R	0.3973	ambiguous	0.3934	ambiguous	-0.826	Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	N
A/S	0.1054	likely_benign	0.0993	benign	-1.275	Destabilizing	0.977	D	0.515	neutral	N	0.463090868	None	None	N
A/T	0.1362	likely_benign	0.1269	benign	-1.198	Destabilizing	0.989	D	0.599	neutral	N	0.466466869	None	None	N
A/V	0.1995	likely_benign	0.1835	benign	-0.428	Destabilizing	0.989	D	0.559	neutral	N	0.460359866	None	None	N
A/W	0.8175	likely_pathogenic	0.7904	pathogenic	-1.322	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
A/Y	0.6331	likely_pathogenic	0.586	pathogenic	-0.902	Destabilizing	1.0	D	0.812	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.