TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6366	19321;19322;19323	chr2:178728942;178728941;178728940	chr2:179593669;179593668;179593667
N2AB	6049	18370;18371;18372	chr2:178728942;178728941;178728940	chr2:179593669;179593668;179593667
N2A	5122	15589;15590;15591	chr2:178728942;178728941;178728940	chr2:179593669;179593668;179593667
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: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-47
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.0828
• 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/D	None	None	1.0	D	0.87	0.727	0.740168519677	gnomAD-4.0.0	6.85068E-07	None	None	None	None	N	None	0	0	None	0	0	None	1.88366E-05	0	0	0	0
A/G	None	None	0.999	D	0.623	0.631	0.57723927602	gnomAD-4.0.0	6.85068E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00155E-07	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	0.8791	likely_pathogenic	0.8492	pathogenic	-1.62	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
A/D	0.9952	likely_pathogenic	0.9966	pathogenic	-2.788	Highly Destabilizing	1.0	D	0.87	deleterious	D	0.638071963	None	None	N
A/E	0.9846	likely_pathogenic	0.9877	pathogenic	-2.58	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
A/F	0.9164	likely_pathogenic	0.9342	pathogenic	-0.883	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
A/G	0.3625	ambiguous	0.4017	ambiguous	-2.061	Highly Destabilizing	0.999	D	0.623	neutral	D	0.592396247	None	None	N
A/H	0.9957	likely_pathogenic	0.9964	pathogenic	-2.157	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
A/I	0.5368	ambiguous	0.4945	ambiguous	-0.339	Destabilizing	0.994	D	0.713	prob.delet.	None	None	None	None	N
A/K	0.9964	likely_pathogenic	0.9971	pathogenic	-1.496	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
A/L	0.5462	ambiguous	0.522	ambiguous	-0.339	Destabilizing	0.994	D	0.671	neutral	None	None	None	None	N
A/M	0.7473	likely_pathogenic	0.7406	pathogenic	-0.71	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
A/N	0.9874	likely_pathogenic	0.9895	pathogenic	-1.847	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
A/P	0.9864	likely_pathogenic	0.9887	pathogenic	-0.72	Destabilizing	1.0	D	0.853	deleterious	D	0.612332047	None	None	N
A/Q	0.9806	likely_pathogenic	0.9838	pathogenic	-1.655	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
A/R	0.9883	likely_pathogenic	0.9901	pathogenic	-1.502	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
A/S	0.5016	ambiguous	0.5243	ambiguous	-2.266	Highly Destabilizing	0.998	D	0.633	neutral	D	0.605195664	None	None	N
A/T	0.5685	likely_pathogenic	0.5598	ambiguous	-1.942	Destabilizing	0.996	D	0.647	neutral	D	0.599886237	None	None	N
A/V	0.2517	likely_benign	0.2276	benign	-0.72	Destabilizing	0.767	D	0.349	neutral	D	0.527640656	None	None	N
A/W	0.9956	likely_pathogenic	0.9963	pathogenic	-1.559	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
A/Y	0.9816	likely_pathogenic	0.9857	pathogenic	-1.131	Destabilizing	1.0	D	0.89	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.