TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9135	27628;27629;27630	chr2:178712519;178712518;178712517	chr2:179577246;179577245;179577244
N2AB	8818	26677;26678;26679	chr2:178712519;178712518;178712517	chr2:179577246;179577245;179577244
N2A	7891	23896;23897;23898	chr2:178712519;178712518;178712517	chr2:179577246;179577245;179577244
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: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-77
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1256
• 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
F/L	None	None	0.055	N	0.675	0.19	0.251116650651	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-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
F/A	0.9017	likely_pathogenic	0.8926	pathogenic	-2.646	Highly Destabilizing	0.272	N	0.755	deleterious	None	None	None	None	N
F/C	0.4523	ambiguous	0.439	ambiguous	-1.878	Destabilizing	0.958	D	0.801	deleterious	N	0.500607487	None	None	N
F/D	0.9855	likely_pathogenic	0.9838	pathogenic	-2.533	Highly Destabilizing	0.726	D	0.841	deleterious	None	None	None	None	N
F/E	0.9895	likely_pathogenic	0.989	pathogenic	-2.334	Highly Destabilizing	0.726	D	0.832	deleterious	None	None	None	None	N
F/G	0.9606	likely_pathogenic	0.9572	pathogenic	-3.083	Highly Destabilizing	0.726	D	0.806	deleterious	None	None	None	None	N
F/H	0.7967	likely_pathogenic	0.8004	pathogenic	-1.648	Destabilizing	0.567	D	0.787	deleterious	None	None	None	None	N
F/I	0.54	ambiguous	0.5078	ambiguous	-1.243	Destabilizing	0.22	N	0.717	prob.delet.	N	0.479238128	None	None	N
F/K	0.9852	likely_pathogenic	0.9857	pathogenic	-1.792	Destabilizing	0.567	D	0.832	deleterious	None	None	None	None	N
F/L	0.9362	likely_pathogenic	0.9329	pathogenic	-1.243	Destabilizing	0.055	N	0.675	prob.neutral	N	0.49975226	None	None	N
F/M	0.8322	likely_pathogenic	0.8225	pathogenic	-1.152	Destabilizing	0.726	D	0.729	prob.delet.	None	None	None	None	N
F/N	0.9329	likely_pathogenic	0.9332	pathogenic	-2.171	Highly Destabilizing	0.726	D	0.842	deleterious	None	None	None	None	N
F/P	0.9968	likely_pathogenic	0.9966	pathogenic	-1.718	Destabilizing	0.89	D	0.835	deleterious	None	None	None	None	N
F/Q	0.9718	likely_pathogenic	0.971	pathogenic	-2.122	Highly Destabilizing	0.726	D	0.849	deleterious	None	None	None	None	N
F/R	0.9593	likely_pathogenic	0.9592	pathogenic	-1.356	Destabilizing	0.567	D	0.845	deleterious	None	None	None	None	N
F/S	0.8671	likely_pathogenic	0.8534	pathogenic	-2.914	Highly Destabilizing	0.497	N	0.797	deleterious	N	0.507969099	None	None	N
F/T	0.9103	likely_pathogenic	0.9013	pathogenic	-2.603	Highly Destabilizing	0.567	D	0.796	deleterious	None	None	None	None	N
F/V	0.5071	ambiguous	0.469	ambiguous	-1.718	Destabilizing	0.22	N	0.735	prob.delet.	N	0.396344599	None	None	N
F/W	0.5048	ambiguous	0.4827	ambiguous	-0.296	Destabilizing	0.726	D	0.701	prob.neutral	None	None	None	None	N
F/Y	0.0711	likely_benign	0.0738	benign	-0.636	Destabilizing	None	N	0.202	neutral	N	0.455617481	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.