TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6258	18997;18998;18999	chr2:178729384;178729383;178729382	chr2:179594111;179594110;179594109
N2AB	5941	18046;18047;18048	chr2:178729384;178729383;178729382	chr2:179594111;179594110;179594109
N2A	5014	15265;15266;15267	chr2:178729384;178729383;178729382	chr2:179594111;179594110;179594109
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: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-46
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.0793
• 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
I/K	rs746617599	-2.194	0.939	D	0.82	0.832	0.926597058261	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-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
I/A	0.8952	likely_pathogenic	0.8943	pathogenic	-2.909	Highly Destabilizing	0.373	N	0.587	neutral	None	None	None	None	N
I/C	0.9073	likely_pathogenic	0.9163	pathogenic	-2.525	Highly Destabilizing	0.996	D	0.798	deleterious	None	None	None	None	N
I/D	0.9947	likely_pathogenic	0.9951	pathogenic	-3.668	Highly Destabilizing	0.953	D	0.829	deleterious	None	None	None	None	N
I/E	0.9871	likely_pathogenic	0.9881	pathogenic	-3.381	Highly Destabilizing	0.953	D	0.822	deleterious	None	None	None	None	N
I/F	0.3509	ambiguous	0.4012	ambiguous	-1.55	Destabilizing	0.91	D	0.687	prob.neutral	None	None	None	None	N
I/G	0.9795	likely_pathogenic	0.98	pathogenic	-3.474	Highly Destabilizing	0.854	D	0.813	deleterious	None	None	None	None	N
I/H	0.9628	likely_pathogenic	0.9681	pathogenic	-3.086	Highly Destabilizing	0.996	D	0.862	deleterious	None	None	None	None	N
I/K	0.968	likely_pathogenic	0.973	pathogenic	-2.275	Highly Destabilizing	0.939	D	0.82	deleterious	D	0.634557338	None	None	N
I/L	0.2196	likely_benign	0.1912	benign	-1.209	Destabilizing	0.164	N	0.395	neutral	D	0.535101581	None	None	N
I/M	0.2246	likely_benign	0.2219	benign	-1.557	Destabilizing	0.939	D	0.662	neutral	D	0.561405831	None	None	N
I/N	0.9294	likely_pathogenic	0.9368	pathogenic	-2.913	Highly Destabilizing	0.953	D	0.859	deleterious	None	None	None	None	N
I/P	0.9922	likely_pathogenic	0.9911	pathogenic	-1.768	Destabilizing	0.984	D	0.852	deleterious	None	None	None	None	N
I/Q	0.9668	likely_pathogenic	0.9707	pathogenic	-2.601	Highly Destabilizing	0.984	D	0.864	deleterious	None	None	None	None	N
I/R	0.9499	likely_pathogenic	0.9583	pathogenic	-2.186	Highly Destabilizing	0.939	D	0.864	deleterious	D	0.634557338	None	None	N
I/S	0.9212	likely_pathogenic	0.9254	pathogenic	-3.47	Highly Destabilizing	0.59	D	0.764	deleterious	None	None	None	None	N
I/T	0.9053	likely_pathogenic	0.9167	pathogenic	-3.038	Highly Destabilizing	0.028	N	0.493	neutral	D	0.601882843	None	None	N
I/V	0.0962	likely_benign	0.0984	benign	-1.768	Destabilizing	0.001	N	0.281	neutral	D	0.537844732	None	None	N
I/W	0.9691	likely_pathogenic	0.9735	pathogenic	-2.042	Highly Destabilizing	0.996	D	0.851	deleterious	None	None	None	None	N
I/Y	0.8791	likely_pathogenic	0.8964	pathogenic	-1.908	Destabilizing	0.953	D	0.795	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.