TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18459	55600;55601;55602	chr2:178601715;178601714;178601713	chr2:179466442;179466441;179466440
N2AB	16818	50677;50678;50679	chr2:178601715;178601714;178601713	chr2:179466442;179466441;179466440
N2A	15891	47896;47897;47898	chr2:178601715;178601714;178601713	chr2:179466442;179466441;179466440
N2B	9394	28405;28406;28407	chr2:178601715;178601714;178601713	chr2:179466442;179466441;179466440
Novex-1	9519	28780;28781;28782	chr2:178601715;178601714;178601713	chr2:179466442;179466441;179466440
Novex-2	9586	28981;28982;28983	chr2:178601715;178601714;178601713	chr2:179466442;179466441;179466440
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-115
• Domain position: 78
• Structural Position: 156
• Q(SASA): 0.0687
• 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/S	None	None	1.0	N	0.875	0.562	0.733087090833	gnomAD-4.0.0	3.19958E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.7326E-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
I/A	0.9553	likely_pathogenic	0.9614	pathogenic	-2.044	Highly Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
I/C	0.9607	likely_pathogenic	0.965	pathogenic	-1.957	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
I/D	0.9994	likely_pathogenic	0.9996	pathogenic	-2.113	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
I/E	0.9978	likely_pathogenic	0.9983	pathogenic	-2.026	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
I/F	0.5859	likely_pathogenic	0.6544	pathogenic	-1.592	Destabilizing	1.0	D	0.832	deleterious	N	0.477999878	None	None	N
I/G	0.9947	likely_pathogenic	0.9958	pathogenic	-2.435	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
I/H	0.9956	likely_pathogenic	0.9968	pathogenic	-1.787	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
I/K	0.9926	likely_pathogenic	0.9945	pathogenic	-1.377	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
I/L	0.2033	likely_benign	0.2119	benign	-0.98	Destabilizing	0.993	D	0.472	neutral	N	0.462441013	None	None	N
I/M	0.3041	likely_benign	0.3129	benign	-1.058	Destabilizing	1.0	D	0.776	deleterious	N	0.467657531	None	None	N
I/N	0.9899	likely_pathogenic	0.9923	pathogenic	-1.476	Destabilizing	1.0	D	0.89	deleterious	N	0.479520815	None	None	N
I/P	0.9981	likely_pathogenic	0.9985	pathogenic	-1.31	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
I/Q	0.9928	likely_pathogenic	0.9945	pathogenic	-1.589	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
I/R	0.9881	likely_pathogenic	0.9912	pathogenic	-0.944	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
I/S	0.987	likely_pathogenic	0.9893	pathogenic	-2.172	Highly Destabilizing	1.0	D	0.875	deleterious	N	0.479267326	None	None	N
I/T	0.9766	likely_pathogenic	0.9799	pathogenic	-1.954	Destabilizing	1.0	D	0.807	deleterious	N	0.479013836	None	None	N
I/V	0.1273	likely_benign	0.1273	benign	-1.31	Destabilizing	0.993	D	0.433	neutral	N	0.449973148	None	None	N
I/W	0.9917	likely_pathogenic	0.9937	pathogenic	-1.755	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
I/Y	0.9683	likely_pathogenic	0.9766	pathogenic	-1.46	Destabilizing	1.0	D	0.803	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.